Miracle-dz/UniFAR-FTUs huggingface dataset:
Functional Evidence for the Presence of Type II 5’-Deiodinase in Somatotropes and Its Adaptive Role in Hypothyroidism

The anterior pituitary contains abundant type II iodothyronine 5′-deiodinase (D2). The role of this enzyme in mediating thyroid hormone action in the pituitary has been proven only for thyrotropes, although there is evidence that it exists in other cell types, including somatotropes and lactotropes. Here we investigated the potential of D2 to mediate thyroid hormone regulation of growth hormone (GH). Using GH mRNA as an end point, we demonstrate that in hyperthyroid states GH mRNA levels are stimulated by triiodothyronine (T3) generated via D1, whereas in hypothyroidism, when D2 activity is markedly increased, GH mRNA is more responsive to tetraiodothyronine (T4) in a propylthiouracil-insensitive, reverse T3-suppressible manner. Under short-term hyperthyroid conditions, GH levels correlate with plasma T3; in contrast, the correlation is not observed in hypothyroidism, a condition in which plasma T3 levels are too low to account for the response. These results add support to the concept that D2 is present in the pituitary and that the enzyme plays an important role in mediating stimulation of GH by thyroid hormones, particularly in hypothyroid states in which they could alleviate the impact of hypothyroxinemia on GH secretion.
Validation of the ITS2 Region as a Novel DNA Barcode for Identifying Medicinal Plant Species

Background The plant working group of the Consortium for the Barcode of Life recommended the two-locus combination of rbcL + matK as the plant barcode, yet the combination was shown to successfully discriminate among 907 samples from 550 species at the species level with a probability of 72%. The group admits that the two-locus barcode is far from perfect due to the low identification rate, and the search is not over. Methodology/Principal Findings Here, we compared seven candidate DNA barcodes (psbA-trnH, matK, rbcL, rpoC1, ycf5, ITS2, and ITS) from medicinal plant species. Our ranking criteria included PCR amplification efficiency, differential intra- and inter-specific divergences, and the DNA barcoding gap. Our data suggest that the second internal transcribed spacer (ITS2) of nuclear ribosomal DNA represents the most suitable region for DNA barcoding applications. Furthermore, we tested the discrimination ability of ITS2 in more than 6600 plant samples belonging to 4800 species from 753 distinct genera and found that the rate of successful identification with the ITS2 was 92.7% at the species level. Conclusions The ITS2 region can be potentially used as a standard DNA barcode to identify medicinal plants and their closely related species. We also propose that ITS2 can serve as a novel universal barcode for the identification of a broader range of plant taxa.
Hedgehog signaling is essential for normal wound healing

The hedgehog family of morphogens (sonic [Shh], Indian, and desert hedgehog) are central regulators of embryologic growth and tissue patterning. Although recent work implicates Shh in postnatal tissue repair and development, conclusive evidence is lacking. Here, we demonstrated the importance of Shh in wound repair, by examining the effects of cyclopamine, a specific inhibitor of the Shh signaling cascade, on tissue repair. Using a murine‐splinted excisional wound model, which attenuates wound contraction in this loose‐skinned rodent, we established that, by all measures (wound closure, epithelialization, granulation formation, vascularity, and proliferation), wound healing was profoundly impaired when Shh signaling was disrupted. Because embryonic disruption of Shh is associated with distinct phenotypic defects, our findings invite investigation of the potential role of Shh signaling under postnatal conditions associated with disregulated wound healing.
Involvement of the GABAergic Septo-Hippocampal Pathway in Brain Stimulation Reward

The hippocampus is a structure related to several cognitive processes, but not very much is known about its putative involvement in positive reinforcement. In its turn, the septum has been related to instrumental brain stimulation reward (BSR) by its electrical stimulation with trains of pulses. Although the anatomical relationships of the septo-hippocampal pathway are well established, the functional relationship between these structures during rewarding behaviors remains poorly understood. To explore hippocampal mechanisms involved in BSR, CA3-evoked field excitatory and inhibitory postsynaptic potentials (fEPSPs, fIPSPs) were recorded in the CA1 area during BSR in alert behaving mice. The synaptic efficiency was determined from changes in fEPSP and fIPSP amplitudes across the learning of a BSR task. The successive BSR sessions evoked a progressive increase of the performance in inverse relationship with a decrease in the amplitude of fEPSPs, but not of fIPSPs. Additionally, we evaluated CA1 local field potentials (LFPs) during a preference task, comparing 8-, 20-, and 100-Hz trains of septal BSR. We corroborate a clear preference for BSR at 100 Hz (in comparison with BSR at 20 Hz or 8 Hz), in parallel with an increase in the spectral power of the low theta band, and a decrease in the gamma. These results were replicated by intrahippocampal injections of a GABAB antagonist. Thus, the GABAergic septo-hippocampal pathway seems to carry information involved in the encoding of reward properties, where GABAB receptors seem to play a key role. With regard to the dorsal hippocampus, fEPSPs evoked at the CA3-CA1 synapse seem to reflect the BSR learning process, while hippocampal rhythmic activities are more related to reward properties.
Joint X-Ray and Optical Measurements of the Mass Distribution of the Distant Galaxy Cluster Cl J0152.7−1357

We present joint X-ray and optical observations of the high-redshift (z ≃ 0.83) lensing cluster Cl J0152.7-1357 made with the Chandra X-Ray Observatory and the Keck telescope. We confirm the existence of significant substructure at both X-ray and optical wavelengths in the form of two distinct clumps, whose temperatures are 6.6 and 5.7 keV, respectively. The X-ray surface brightness profiles of the two clumps can be fitted by either a single β-model or an NFW-like profile, the latter giving better fits to the central regions. We find that the X-ray–derived mass of this cluster is in good agreement with independent lensing measurements. While its appearance indicates that the cluster has not reached a dynamical equilibrium state, its X-ray luminosity LX, temperature T, and dynamical mass M are consistent with the well-defined LX-T and M-T relations for low-redshift galaxy clusters, which suggests that the dynamical properties of the clusters have remained almost unchanged since z ≈ 0.8.
A Randomized, Controlled Trial of Manual Therapy and Specific Adjuvant Exercise for Chronic Low Back Pain

Objective:This article examines the effectiveness of manual therapy with specific adjuvant exercise for treating chronic low back pain and disability. Methods:A single blind, randomized, controlled trial was employed. Patients were prescribed an exercise program that was tailored to treat their musculoskeletal dysfunctions or given a nonspecific program of general stretching and aerobic conditioning. In addition, patients received manual therapy or sham manual therapy. Participants were seen for 6 weekly sessions and were asked to perform their exercise program twice daily. Results:Seventy-two out of 100 patients completed the study. Multivariate tests conducted for measures of pain and disability revealed a significant group by time interaction (P = 0.04 and P = 0.05, respectively), indicating differential change in these measures pretreatment to posttreatment as a function of the treatment received. When controlling for pretreatment scores, patients receiving manual therapy with specific adjuvant exercise reported significant reductions in pain. No change in perceived disability was observed, with the exception that patients receiving sham manual therapy with specific adjuvant exercise reported significantly greater disability at posttreatment. Discussion:Manual therapy with specific adjuvant exercise appears to be beneficial in treating chronic low back pain. Despite changes in pain, perceived function did not improve. It is possible that impacting chronic low back pain alone does not address psychosocial or other factors that may contribute to disability. Further studies are needed to examine the long-term effects of these interventions and to address what adjuncts are beneficial in improving function in this population.
Efficacy of acetic acid‐spraying method in diagnosing extension of barrett's cancer under the squamous epithelium

Aim: Endoscopic diagnosis of the lateral extension of Barrett's cancer under the squamous epithelium (BCUS) is sometimes difficult because the cancer is unobservable in the esophageal lumen. The aim of the present study was to clarify the endoscopic features of the extension of BCUS and verify the usefulness of the acetic acid‐spraying method (AAS) for diagnosis.
Accelerating SystemC simulations using GPUs

Recent developments in graphics processing unit (GPU) technology has invigorated an interest in using GPUs for accelerating the simulation of SystemC models. SystemC is extensively used for design space exploration, and early performance analysis of hardware systems. SystemC's reference implementation of the simulation kernel supports a single-threaded simulation kernel. However, modern computing platforms offer substantially more compute power by means of multiple central processing units, and multiple co-processors such as GPUs. This has peaked an interest in parallelizing SystemC simulations. Of these, several efforts focus on utilizing the massive parallelism offered by GPUs as an alternate computing platform. In this paper, we present a summary of these recent research efforts that propose using GPUs for accelerating SystemC simulation.
Neocortical neurogenesis in humans is restricted to development

Stem cells generate neurons in discrete regions in the postnatal mammalian brain. However, the extent of neurogenesis in the adult human brain has been difficult to establish. We have taken advantage of the integration of 14C, generated by nuclear bomb tests during the Cold War, in DNA to establish the age of neurons in the major areas of the human cerebral neocortex. Together with the analysis of the neocortex from patients who received BrdU, which integrates in the DNA of dividing cells, our results demonstrate that, whereas nonneuronal cells turn over, neurons in the human cerebral neocortex are not generated in adulthood at detectable levels but are generated perinatally.
Faults in linux: ten years later

In 2001, Chou et al. published a study of faults found by applying a static analyzer to Linux versions 1.0 through 2.4. 1. A major result of their work was that the drivers directory contained up to 7 times more of certain kinds of faults than other directories. This result inspired a number of development and research efforts on improving the reliability of driver code. Today Linux is used in a much wider range of environments, provides a much wider range of services, and has adopted a new development and release model. What has been the impact of these changes on code quality? Are drivers still a major problem? To answer these questions, we have transported the experiments of Chou et al. to Linux versions 2.6. 0 to 2.6. 33, released between late 2003 and early 2010. We find that Linux has more than doubled in size during this period, but that the number of faults per line of code has been decreasing. And, even though drivers still accounts for a large part of the kernel code and contains the most faults, its fault rate is now below that of other directories, such as arch (HAL) and fs (file systems). These results can guide further development and research efforts. To enable others to continually update these results as Linux evolves, we define our experimental protocol and make our checkers and results available in a public archive.
Genome Trees from Conservation Profiles

The concept of the genome tree depends on the potential evolutionary significance in the clustering of species according to similarities in the gene content of their genomes. In this respect, genome trees have often been identified with species trees. With the rapid expansion of genome sequence data it becomes of increasing importance to develop accurate methods for grasping global trends for the phylogenetic signals that mutually link the various genomes. We therefore derive here the methodological concept of genome trees based on protein conservation profiles in multiple species. The basic idea in this derivation is that the multi-component “presence-absence” protein conservation profiles permit tracking of common evolutionary histories of genes across multiple genomes. We show that a significant reduction in informational redundancy is achieved by considering only the subset of distinct conservation profiles. Beyond these basic ideas, we point out various pitfalls and limitations associated with the data handling, paving the way for further improvements. As an illustration for the methods, we analyze a genome tree based on the above principles, along with a series of other trees derived from the same data and based on pair-wise comparisons (ancestral duplication-conservation and shared orthologs). In all trees we observe a sharp discrimination between the three primary domains of life: Bacteria, Archaea, and Eukarya. The new genome tree, based on conservation profiles, displays a significant correspondence with classically recognized taxonomical groupings, along with a series of departures from such conventional clusterings.
Relief of dysphagia during neoadjuvant treatment for cancer of the esophagus or gastroesophageal junction.

Dysphagia is the main symptom of cancer of the esophagus and gastroesophageal junction and causing nutritional problems and weight loss, often counteracted by insertion of self-expandable metal stents or nutrition via an enteral route. Clinical observations indicate that neoadjuvant therapy may effectively and promptly alleviate dysphagia, making such nutrition supportive interventions redundant before surgical resection. The objective of the current study was to carefully study the effects of induction neoadjuvant therapy on dysphagia and its subsequent course and thereby investigate the actual need for alimentary gateways for nutritional support. Thirty-five consecutive patients scheduled for neoadjuvant therapy were recruited and assessed regarding dysphagia and appetite at baseline, after the first cycle of preoperative treatment with either chemotherapy alone or with chemoradiotherapy and before surgery. Platinum-based therapy in combination with 5-fluorouracil was administered intravenously days 1-5 every 3 weeks and consisted of three treatments. Patients receiving combined chemoradiotherapy started radiotherapy on day one of second chemotherapy cycle. They received fractions of 2 Gy/day each up to a total dose of 40 Gy. Watson and Ogilvie dysphagia scores were used to assess dysphagia, while appetite was assessed by the Edmonton Assessment System Visual analogue scale-appetite questionnaire. Patients were evaluated at regular outpatient clinic visits or by telephone. The histological tumor response in the surgical specimen was assessed using the Chirieac scale. Ten patients scheduled for neoadjuvant chemotherapy and 25 patients scheduled for chemoradiotherapy were included in the analysis. There was a significant improvement in dysphagia in both treatment groups, according to both scales, already from baseline to the completion of the first chemotherapy cycle which remained to the end of the neoadjuvant treatment (P < 0.001). Appetite also improved after the first chemotherapy cycle (P = 0.03). Body weight did not change during any type of neoadjuvant therapy. We were unable to demonstrate any association between relief of dysphagia and the degree of histological response to neoadjuvant therapy in the surgical specimen. The present study shows that a platin - 5FU-based neoadjuvant chemotherapy, with or without concomitant radiotherapy, effectively and promptly relieves dysphagia in patients presenting with cancers of the esophagus or gastroesophageal junction already after the first cycle.
Medical physics practice in the next decade

Impressive advances in computers and materials science have fueled a broad-based confluence of basic science breakthroughs. These advances are making us reformulate our learning, teaching and credentialing methodologies and research and development frontiers. We are now in the age of molecular medicine. In the entire field of health care, a paradigm shift from population-based solutions to individual specific care is taking place. These trends are reshaping the practice of medical physics. In this short presentation, examples are given to illustrate developments in image-guided intensity-modulated and adaptive helical tomotherapy, enhanced application of intensity modulation radiotherapy (IMRT) using adaptive radiotherapy and conformal avoidance. These advances include improved normal tissue sparing and permit dose reconstruction and verification, thereby allowing significant biologically effective dose escalation and reduced radiation toxicity. The intrinsic capability of helical TomoTherapy for megavoltage CT imaging for IMRT image-guidance is also discussed. Finally developments in motion management are described.
Peripartum Cardiomyopathy: Current State of Knowledge, New Developments and Future Directions

Peripartum cardiomyopathy (PPCM) is a form of idiopathic dilated cardiomyopathy affecting women in late pregnancy or early puerperium. Although initially described in the late 1800s, it has only recently been recognized as a distinct cardiac condition. The reported incidence and prognosis varies according to geography. The clinical course varies between complete recovery to rapid progression to chronic heart failure, heart transplantation or death. In spite of significant improvements in understanding the pathophysiology and management of the PPCM many features of this unique disease are poorly understood, including incidence, etiology, epidemiology, pathophysiology, predictors of prognosis and optimal therapy. The present article revisits these concepts and recent advances in PPCM.
Investigation of a pseudo-outbreak of ‘Pseudomonas thomasii’ in a special-care baby unit by numerical analysis of SDS–PAGE protein patterns

SUMMARY Forty-two cultures of pseudomonas comprising 28 clinical isolates from a pseudo-outbreak on a Special-Care Baby Unit and 14 reference strains, including 9 type strains, of various Pseudomonas species, were characterized by one-dimensional sodium dodecyl sulphate–polyacrylamide gel electrophoresis (SDS–PAGE) of whole-cell proteins. The protein patterns were highly reproducible and were used as the basis for a numerical analysis which divided the strains into 9 phenons. Two of the 28 clinical isolates were identified by biochemical tests as P. pickettii and their identification was confirmed by SDS–PAGE as they fell in the same phenon as the type strain of the species. The remaining 26 isolates, which could not be identified on phenotypic tests, fell in the same phenon as three reference strains of ‘P. thomasii’. The protein patterns provided the first clear evidence that P. pickettii and ‘P. thomasii’ were separate taxa and that the ‘outbreak’ was polymicrobial in origin, in line with the probable aqueous source of contamination. We conclude that high-resolution SDS–PAGE of proteins provides an effective method of identifying and differentiating pseudomonads, especially where this cannot be done adequately using conventional biochemical tests.
Human Pavlovian–Instrumental Transfer

The vigor with which a participant performs actions that produce valuable outcomes is subject to a complex set of motivational influences. Many of these are believed to involve the amygdala and the nucleus accumbens, which act as an interface between limbic and motor systems. One prominent class of influences is called pavlovian–instrumental transfer (PIT), in which the motivational characteristics of a predictor influence the vigor of an action with respect to which it is formally completely independent. We provide a demonstration of behavioral PIT in humans, with an audiovisual predictor of the noncontingent delivery of money inducing participants to perform more avidly an action involving squeezing a handgrip to earn money. Furthermore, using functional magnetic resonance imaging, we show that this enhanced motivation was associated with a trial-by-trial correlation with the blood oxygenation level-dependent (BOLD) signal in the nucleus accumbens and a subject-by-subject correlation with the BOLD signal in the amygdala. Our data dovetails well with the animal literature and sheds light on the neural control of vigor.
Effect of Clay Dispersion on Mechanical, Thermal and Vibration Properties of Glass Fiber-Reinforced Vinyl Ester Composites

Glass fiber reinforced vinyl ester polymer composites filled with clay particles were synthesized by a hand lay-up technique with the addition of methy ethyl ketone peroxide (MEKP), cobalt napthalate and benzoyl peroxide. Mechanical and thermal properties of vinyl ester-glass fiber composite and clay particles dispersed vinyl-glass fiber hybrids were investigated in the present work. The hybridization effect of nanoclay dispersion in vinyl ester-fiber composite was discussed. Enhanced mechanical, thermal and vibration properties were observed in nanoclay dispersed composites over vinyl ester-glass fiber composite.
Brain-derived neurotrophic factor: role in depression and suicide

Depression and suicidal behavior have recently been shown to be associated with disturbances in structural and synaptic plasticity. Brain-derived neurotrophic factor (BDNF), one of the major neurotrophic factors, plays an important role in the maintenance and survival of neurons and in synaptic plasticity. Several lines of evidence suggest that BDNF is involved in depression, such that the expression of BDNF is decreased in depressed patients. In addition, antidepressants up-regulate the expression of BDNF. This has led to the proposal of the “neurotrophin hypothesis of depression”. Increasing evidence demonstrates that suicidal behavior is also associated with lower expression of BDNF, which may be independent from depression. Recent genetic studies also support a link of BDNF to depression/suicidal behavior. Not only BDNF, but abnormalities in its cognate receptor tropomycin receptor kinase B (TrkB) and its splice variant (TrkB.T1) have also been reported in depressed/suicidal patients. It has been suggested that epigenetic modulation of the Bdnf and Trkb genes may contribute to their altered expression and functioning. More recently, impairment in the functioning of pan75 neurotrophin receptor has been reported in suicide brain specimens. pan75 neurotrophin receptor is a low-affinity neurotrophin receptor that, when expressed in conjunction with low availability of neurotropins/Trks, induces apoptosis. Overall, these studies suggest the possibility that BDNF and its mediated signaling may participate in the pathophysiology of depression and suicidal behavior. This review focuses on the critical evidence demonstrating the involvement of BDNF in depression and suicide.