Miracle-dz/UniFAR-FTUs huggingface dataset:
Multidisciplinary treatment of brain metastases derived from clear cell renal cancer incorporating stereotactic radiosurgery

Brain metastases are a frequent complication in patients with metastatic clear cell renal cancer. Survival after whole‐brain radiotherapy (WBRT) is disappointing. A retrospective analysis of multimodality treatment was performed in patients who had received linear accelerator (LINAC)‐based stereotactic radiosurgery (SRS).
Velocity autocorrelation functions of hard-sphere fluids: Long-time tails upon undercooling

Molecular dynamics simulations are employed to obtain the velocity autocorrelation function (VAF) for hard spheres, spanning a wide range of volume fractions from dilute to high-density metastable fluids. For all volume fractions below freezing, Alder's classical positive 3/2 long-time tail is observed. For volume fractions from 0.45 to 0.48 the VAF becomes negative, before becoming positive and decaying with the positive 3/2 long-time tail. At the freezing volume fraction (0.494) the Alder 3/2 tail is not observed. At higher volume fractions a negative tail with an exponent of 5/2 emerges, which coincides with the long-time tail of a Lorentz gas.
The Role of Endogenous IFN-β in the Regulation of Th17 Responses in Patients with Relapsing-Remitting Multiple Sclerosis

IFN-β has been used as a first-line therapy for relapsing-remitting multiple sclerosis (RRMS). Because only a few studies have addressed the role of endogenous IFN-β in the pathogenesis of the disease, our objective was to characterize its role in the transcriptional regulation of pathogenic Th17 cytokines in patients with RRMS. In vitro studies have demonstrated that IFN-β inhibits IL-17A, IL-17F, IL-21, IL-22, and IFN-γ secretion in CD4+ lymphocytes through the induction of suppressor of cytokine secretion 1 and suppressor of cytokine secretion 3. We found that patients with RRMS have increased serum and cerebrospinal fluid Th17 (IL-17A and IL-17F) cytokine levels in comparison with the control subjects, suggesting that deficient endogenous IFN-β secretion or signaling can contribute to the dysregulation of those pathogenic cytokines in CD4+ cells. We identified that the endogenous IFN-β from serum of RRMS patients induced a significantly lower IFN-inducible gene expression in comparison with healthy controls. In addition, in vitro studies have revealed deficient endogenous and exogenous IFN-β signaling in the CD4+ cells derived from patients with MS. Interestingly, upon inhibition of the endogenous IFN-β signaling by silencing IFN regulatory factor (IRF) 7 gene expression, the resting CD4+ T cells secreted significantly higher level of IL-17A, IL-17F, IL-21, IL-22, and IL-9, suggesting that endogenous IFN-β suppresses the secretion of these pathogenic cytokines. In vivo recombinant IFN-β–1a treatment induced IFNAR1 and its downstream signaling molecules’ gene expression, suggesting that treatment reconstitutes a deficient endogenous IFN-β regulation of the CD4+ T cells’ pathogenic cytokine production in patients with MS.
Modulation of muscle–tendon interaction in the human triceps surae during an energy dissipation task

ABSTRACT The compliance of elastic elements allows muscles to dissipate energy safely during eccentric contractions. This buffering function is well documented in animal models but our understanding of its mechanism in humans is confined to non-specific tasks, requiring a subsequent acceleration of the body. The present study aimed to examine the behaviour of the human triceps surae muscle–tendon unit (MTU) during a pure energy dissipation task, under two loading conditions. Thirty-nine subjects performed a single-leg landing task, with and without added mass. Ultrasound measurements were combined with three-dimensional kinematics and kinetics to determine instantaneous length changes of MTUs, muscle fascicles, Achilles tendon and combined elastic elements. Gastrocnemius and soleus MTUs lengthened during landing. After a small concentric action, fascicles contracted eccentrically during most of the task, whereas plantar flexor muscles were activated. Combined elastic elements lengthened until peak ankle moment and recoiled thereafter, whereas no recoil was observed for the Achilles tendon. Adding mass resulted in greater negative work and MTU lengthening, which were accompanied by a greater stretch of tendon and elastic elements and a greater recruitment of the soleus muscle, without any further fascicle strain. Hence, the buffering action of elastic elements delimits the maximal strain and lengthening velocity of active muscle fascicles and is commensurate with loading constraints. In the present task, energy dissipation was modulated via greater MTU excursion and more forceful eccentric contractions. The distinct strain pattern of the Achilles tendon supports the notion that different elastic elements may not systematically fulfil the same function. Summary: During a simple landing task, the compliance of elastic structures and muscle activity modulate energy absorption and dissipation via active lengthening of the triceps surae fascicles.
Tau is not normally degraded by the proteasome

Tau‐positive inclusions in neurons are consistent neuropathologic features of the most common causes of dementias such Alzheimer's disease and frontotemporal dementia. Ubiquitinated tau‐positive inclusions have been reported in brains of Alzheimer's disease patients, but involvement of the ubiquitin‐dependent proteasomal system in tau degradation remains controversial. Before considering the tau degradation in pathologic conditions, it is important to determine whether or not endogenous tau is normally degraded by the proteasome pathway. We therefore investigated this question using two complementary approaches in vitro and in vivo. Firstly, SH‐SY5Y human neuroblastoma cells were treated with different proteasome inhibitors, MG132, lactacystin, and epoxomicin. Under these conditions, neither total nor phosphorylated endogenous tau protein levels were increased. Instead, an unexpected decrease of tau protein was observed. Secondly, we took advantage of a temperature‐sensitive mutant allele of the 20S proteasome in Drosophila. Genetic inactivation of the proteasome also resulted in a decrease of tau levels in Drosophila. These results obtained in vitro and in vivo demonstrate that endogenous tau is not normally degraded by the proteasome. © 2005 Wiley‐Liss, Inc.
On the Distinction between Unethical and Selfish Behavior

Does unethical behavior always represent selfish behavior? Consider the seminal dilemma that serves as the foundation for modern moral psychology: The wife of a man named Heinz was near death and desperate for a medicine that he could not afford (Kohlberg, 1963). To save her life, Heinz broke into a drugstore to steal the medicine. Kohlberg asked his subjects, “Should Heinz have stolen for his dying wife? Why or why not? ” Whereas Kohlberg was interested in how people reasoned through this moral dilemma, we were instead struck by the fact that Heinz stole not to help himself, but to assist another person. Heinz might have acted unethically, but did he act selfishly? Or consider the contemporary case of Aaron Swartz. As a computer programmer, Swartz downloaded 4.8 million articles from the journal database JSTOR and made them publicly available. Although his action clearly violated computer and copyright laws, his alleged intention was “to place the material on the Internet so that it could be freely distributed around the entire globe” (Abelson, Diamond, Grosso, & Pfeiffer, 2013, p. 31). Oftentimes, to act unethically is to act selfishly. Indeed, the bulk of ancient Greek philosophy and modern moral psychology has studied how individuals resolve moral dilemmas in which “doing the right thing” and acting in one’s self-interest are in conflict (Bazerman & Gino, 2012). In fact, Plato (trans. 1997) himself believed that selfinterest lies at the root of all unethical behaviors: “the cause of each and every crime Is unethical behavior always selfish, and is selfish behavior always unethical?
IL-4/IL-13 Signaling Inhibits the Potential of Early Thymic Progenitors To Commit to the T Cell Lineage

Early thymic progenitors (ETPs) are endowed with diverse potencies and can give rise to myeloid and lymphoid lineage progenitors. How the thymic environment guides ETP commitment and maturation toward a specific lineage remains obscure. We have previously shown that ETPs expressing the heteroreceptor (HR) comprising IL-4Rα and IL-13Rα1 give rise to myeloid cells but not T cells. In this article, we show that signaling through the HR inhibits ETP maturation to the T cell lineage but enacts commitment toward the myeloid cells. Indeed, HR+ ETPs, but not HR− ETPs, exhibit activated STAT6 transcription factor, which parallels with downregulation of Notch1, a critical factor for T cell development. Meanwhile, the myeloid-specific transcription factor C/EBPα, usually under the control of Notch1, is upregulated. Furthermore, in vivo inhibition of STAT6 phosphorylation restores Notch1 expression in HR+ ETPs, which regain T lineage potential. In addition, upon stimulation with IL-4 or IL-13, HR− ETPs expressing virally transduced HR also exhibit STAT6 phosphorylation and downregulation of Notch1, leading to inhibition of lymphoid, but not myeloid, lineage potential. These observations indicate that environmental cytokines play a role in conditioning ETP lineage choice, which would impact T cell development.
Historical Review of Trials With Vinorelbine in Non-Small-Cell Lung Cancer

Two large-scale, randomized, phase III trials have offered new information on the response rates, survival benefits, and safety profile of vinorelbine (Navelbine) in non-small-cell lung cancer (NSCLC). In a multicenter, European trial, the response rate was significantly higher with vinorelbine/cisplatin (Platinol) than with vindesine (Eldisine)/cisplatin (P < .02) or vinorelbine alone (P < .001).
Numerical simulation of a possible origin of the positive radial metallicity gradient of the thick disk

We analyze the radial and vertical metallicity and [α/Fe] gradients of the disk stars of a disk galaxy simulated in a fully cosmological setting with the chemo-dynamical galaxy evolution code GCD+. We study how the radial abundance gradients vary as a function of height above the plane and find that the metallicity ([α/Fe]) gradient becomes more positive (negative) with increasing height, changing sign around 1.5 kpc above the plane. At the largest vertical height (2 < |z| < 3 kpc), our simulated galaxy shows a positive radial metallicity gradient. We find that the positive metallicity gradient is caused by the age-metallicity and age-velocity dispersion relation, where younger stars have higher metallicity and lower velocity dispersion. Due to the age-velocity dispersion relation, a greater fraction of younger stars reaches |z| > 2 kpc at the outer region, because of the lower gravitational restoring force of the disk, i.e. flaring. As a result, the fraction of younger stars with higher metallicity due to the age-metallicity relation becomes higher at the outer radii, which makes the median metallicity higher at the outer radii. Combining this result with the recently observed age-metallicity and age-velocity dispersion relation for the Milky Way thick disk stars suggested by Haywood et al., we argue that the observed (small) positive radial metallicity gradient at large heights of the Milky Way disk stars can be explained by flaring of the younger thick and/or thin disk stars.
Higher bone mineral density is associated with a decreased risk of colorectal adenomas

Bone mineral density (BMD) is a biomarker for cumulative exposure to multiple factors including estrogen, calcium, vitamin D and physical activity, which have all been independently associated with colorectal cancer. Furthermore, higher levels of BMD have been inversely associated with colorectal cancer risk, particularly in postmenopausal women. However, no prior studies have examined the potential association between BMD and colorectal adenomas, which are precursor lesions to most colorectal cancers. Therefore, we evaluated the association between BMD, which was measured using a whole body, dual‐energy X‐ray absorptiometry scan and colorectal adenomas in 167 patients who underwent colonoscopy screening. We found that patients in the highest tertile of total body BMD (>1.294 g/cm2) and in the middle tertile (≥1.167 to ≤1.294 g/cm2) compared to those with a total body BMD in the lowest tertile (<1.167 g/cm2) had a lower risk of colorectal adenomas (highest vs. lowest tertile: OR = 0.29 (0.10–0.84); middle vs. lowest tertile: OR = 0.26 (0.08–0.80); p‐trend = 0.02). Stratification by gender revealed that this association was more pronounced in women (highest (>1.280 g/cm2) vs. lowest (<1.130 g/cm2) tertile: OR = 0.08 (0.01–0.70); middle (≥1.130 to ≤1.280 g/cm2) vs. lowest tertile: OR = 0.15 (0.04–0.94); p‐trend = 0.02) even after excluding hormone replacement therapy users (highest (>1.295 g/cm2) and middle (≥1.132 to ≤1.295 g/cm2) vs. lowest (<1.132 g/cm2) tertile: OR = 0.17 (0.03–0.97); p‐trend = 0.04). Our results show, for the first time, that BMD is inversely associated with colorectal adenomas, particularly in women. Although additional larger, prospective studies are needed, our results suggest that BMD may be a biomarker for colorectal cancer precursor lesions.
High-density-lipoprotein cholesterol and types of alcoholic beverages consumed among men and women.

OBJECTIVES Differences by sex in the relationship between high-density-lipoprotein (HDL) cholesterol and consumption of alcoholic beverages were examined in 1516 individuals. METHODS Questionnaires and blood-sample data from cross-sectional surveys were analyzed. RESULTS Both beer and liquor were independently associated with increased HDL cholesterol in the total group, in men, and in women after covariates were controlled for. Wine was associated with a significant increase in HDL cholesterol in women only. CONCLUSIONS Among women and men, amount may be more important than type of alcoholic beverage consumed. The independent effect of wine on HDL cholesterol among men remains unclear since few men in this population consumed wine exclusively or in large quantities.
Effect of pressure on the superconducting Tc of lanthanum.

The effect of pressure on the superconducting transition temperature Tc of La was studied up to 50 GPa. Tc(P) shows a rather complicated variation with a discontinuous increase in Tc at about 2.2 GPa due to the first-order phase transition from dhcp to fcc structure. At about 5.4 GPa a sharp peak is observed due to the soft-mode phase transition from fcc to the distorted fcc structure and two broad maxima are found within the stability region of the distorted fcc structure around 12 and 39 GPa. Some differences between these and previous low-pressure data for metastable fcc La are noticed. The results are discussed in connection with pressure-induced structural phase transitions found in earlier x-ray-diffraction experiments and band-structure calculations giving evidences for van Hove singularities in the density of states.
Cellular and subcellular patterns of expression of bFGF and CNTF in the normal and light stressed adult rat retina.

This study compared the distributions in the normal and light stressed rat retina of the neuroprotective factors bFGF (basic fibroblast growth factor) and CNTF (ciliary neurotrophic factor). Albino Sprague-Dawley rats were raised in cyclic light and some were exposed to bright continuous light for 48 hr, to induce light damage of photoreceptors. Their retinas were prepared as cryosections, immunolabelled with antibodies to bFGF and CNTF and analysed by confocal microscopy. Both factors were prominent in macroglial cells (astrocytes, Müller cells) and the retinal pigment epithelium (RPE). In the somas of these cells the distributions of the two factors were complementary, with bFGF concentrated in the nuclei and CNTF in the cytoplasm. Both factors were distributed along the processes of macroglial cells, in granular form. CNTF was not detected in neurones, but bFGF was consistently present in the cytoplasm of ganglion cell somas and, in regions of retina subject to stress, in the cytoplasm of photoreceptors. bFGF was not detected in the nuclei or processes of neurones. In retina stressed by light exposure or proximity to the anterior edge of the retina, the levels of bFGF and CNTF were up-regulated, without major changes in localization. Macroglial cells (Müller cells, astrocytes) play a major role in distributing bFGF and CNTF throughout the retina. The different localizations of the two factors within the somas of macroglial, RPE and photoreceptor cells, suggest that their protective actions are exerted by distinctive mechanisms.
Substrate Specificities of Recombinant Mannan-binding Lectin-associated Serine Proteases-1 and -2*

Mannan-binding lectin (MBL)-associated serine proteases-1 and 2 (MASP-1 and MASP-2) are homologous modular proteases that each interact with MBL, an oligomeric serum lectin involved in innate immunity. To precisely determine their substrate specificity, human MASP-1 and MASP-2, and fragments from their catalytic regions were expressed using a baculovirus/insect cells system. Recombinant MASP-2 displayed a rather wide, C1s-like esterolytic activity, and specifically cleaved complement proteins C2 and C4, with relative efficiencies 3- and 23-fold higher, respectively, than human C1s. MASP-2 also showed very weak C3 cleaving activity. Recombinant MASP-1 had a lower and more restricted esterolytic activity. It showed marginal activity toward C2 and C3, and no activity on C4. The enzymic activity of both MASP-1 and MASP-2 was specifically titrated by C1 inhibitor, and abolished at a 1:1 C1 inhibitor:protease ratio. Taken together with previous findings, these and other data strongly support the hypothesis that MASP-2 is the protease that, in association with MBL, triggers complement activation via the MBL pathway, through combined self-activation and proteolytic properties devoted to C1r and C1s in the C1 complex. In view of the very low activity of MASP-1 on C3 and C2, our data raise questions about the implication of this protease in complement activation.
A New Creep Constitutive Model for Eutectic Solder Alloy

In this study, a large number of creep tests were carried out to study the effect of stress level and testing temperature on the creep behavior of 63 Sn/37Pb solder in a systematic manner. Based on the dislocation controlled creep mechanism and Gibbs’ free-energy theory, a new creep constitutive model was proposed. The model was found to describe accurately the creep flow of the solder and to be capable of explaining the issues of stress and temperature dependent stress exponent and activation energy in the Arrhenius powerlaw creep model. Furthermore, the model was employed to predict accurately the longterm reliability of solder joints in a PBGA assembly. @DOI: 10.1115/1.1462624#
A direct interview family study of obsessive–compulsive disorder. I

Background. This and the companion paper present two sequential family studies of obsessive–compulsive disorder (OCD) conducted by the same research group, but with different sampling and best-estimate procedures. In addition to providing further data on familial transmission of OCD, we used comparison of disparate findings (moderate, specific familial aggregation in this first study versus a stronger effect for other anxiety disorders than for OCD alone in the second) to examine possible effects of proband characteristics and informant data on outcome. Method. In this initial study we interviewed 179 first-degree relatives of 72 OCD probands and 112 relatives of 32 never mentally ill (NMI) controls. Informant data were obtained on an additional 126 relatives (total ‘combined’ samples of 263 and 154 respectively). Analyses used best-estimate diagnoses made by consensus of two ‘blinded’ senior clinicians who reviewed all diagnostic materials including proband informant data about relatives. Results. Significantly higher risk for OCD but not other anxiety disorders was found in relatives of OCD probands compared to relatives of controls in both the directly interviewed and combined samples. There was no relationship between proband age at onset of OCD and strength of familial aggregation. Conclusions. These data indicate moderate familial aggregation of OCD, but do not support increased transmission by early onset probands, or a familial relationship between OCD and other anxiety disorders with the possible exception of generalized anxiety disorder.
Effects of Vestibular Rehabilitation on Balance Control in Older People with Chronic Dizziness: A Randomized Clinical Trial

Objective The aim of this study was to compare the effects of vestibular rehabilitation protocols on balance control in elderly with dizziness. Design This is a randomized clinical trial with 3-mo follow-up period. The sample was composed of 82 older individuals with chronic dizziness from vestibular disorders. The control group was treated according to the Conventional Cawthorne & Cooksey protocol (n = 40), and the experimental group was submitted to a Multimodal Cawthorne & Cooksey protocol (n = 42). Measures included Dynamic Gait Index, fall history, hand grip strength, Time Up-and-Go Test, sit-to-stand test, multidirectional reach, and static balance tests. Results With the exception of history of falls, Forward Functional Reach, Unipedal Right and Left Leg Eyes Closed, and Sensorial Romberg Eyes Open, all outcomes improved after treatments. Such results persisted at follow-up period, with the exception of the Tandem Eyes Open and the Timed Up-and-Go manual. The between-group differences for Sensorial Romberg Eyes Closed (4.27 secs) and Unipedal Left Leg Eyes Open (4.08 secs) were significant after treatment, favoring the Multimodal protocol. Conclusions Both protocols resulted in improvement on elderly’s balance control, which was maintained during a short-term period. The multimodal protocol presented better performance on specific static balance tests.
Seniors' experiences with online banking

Older adults are the fastest growing segment of the population worldwide. This paper presents a evaluation of the user experience of two online web-banking sites from an older user's point of view. We therefore conducted a usability testing employing 12 older participants, in order to analyze the needs and issues faced by this user group when performing real-world tasks. The study involved six tasks which users were required to complete within a specific time. Most of the participants were interested in learning to use online banking. Our results show that older persons do not find web-banking sites easy or user-friendly. Our qualitative findings revealed that both of the web-banking sites we examined presented problems. Implications for the future include the need to redesign bank websites so as to include guidelines and other suggestions made in this study.