Miracle-dz/UniFAR-FTUs huggingface dataset:
Leucine-rich Repeat Kinase 2 (LRRK2) Pharmacological Inhibition Abates α-Synuclein Gene-induced Neurodegeneration*

Background: LRRK2 kinase activity has been implicated in Parkinson disease (PD). Results: LRRK2 kinase inhibition attenuated neurodegeneration in LRRK2 transgenic and wild-type rats. Conclusion: Chronic inhibition of LRRK2 kinase activity is well tolerated in rats and provides neuroprotection from α-synuclein overexpression. Significance: These results warrant further studies that test the therapeutic potential of LRRK2 kinase inhibitors in additional PD models. Therapeutic approaches to slow or block the progression of Parkinson disease (PD) do not exist. Genetic and biochemical studies implicate α-synuclein and leucine-rich repeat kinase 2 (LRRK2) in late-onset PD. LRRK2 kinase activity has been linked to neurodegenerative pathways. However, the therapeutic potential of LRRK2 kinase inhibitors is not clear because significant toxicities have been associated with one class of LRRK2 kinase inhibitors. Furthermore, LRRK2 kinase inhibitors have not been tested previously for efficacy in models of α-synuclein-induced neurodegeneration. To better understand the therapeutic potential of LRRK2 kinase inhibition in PD, we evaluated the tolerability and efficacy of a LRRK2 kinase inhibitor, PF-06447475, in preventing α-synuclein-induced neurodegeneration in rats. Both wild-type rats as well as transgenic G2019S-LRRK2 rats were injected intracranially with adeno-associated viral vectors expressing human α-synuclein in the substantia nigra. Rats were treated with PF-06447475 or a control compound for 4 weeks post-viral transduction. We found that rats expressing G2019S-LRRK2 have exacerbated dopaminergic neurodegeneration and inflammation in response to the overexpression of α-synuclein. Both neurodegeneration and neuroinflammation associated with G2019S-LRRK2 expression were mitigated by LRRK2 kinase inhibition. Furthermore, PF-06447475 provided neuroprotection in wild-type rats. We could not detect adverse pathological indications in the lung, kidney, or liver of rats treated with PF-06447475. These results demonstrate that pharmacological inhibition of LRRK2 is well tolerated for a 4-week period of time in rats and can counteract dopaminergic neurodegeneration caused by acute α-synuclein overexpression.
Mammals across the K/Pg boundary in northeastern Montana, U.S.A.: dental morphology and body-size patterns reveal extinction selectivity and immigrant-fueled ecospace filling

Abstract The Cretaceous/Tertiary (K/Pg) mass extinction has long been viewed as a pivotal event in mammalian evolutionary history, in which the extinction of non-avian dinosaurs allowed mammals to rapidly expand from small-bodied, generalized insectivores to a wide array of body sizes and ecological specializations. Many studies have used global- or continental-scale taxonomic databases to analyze this event on coarse temporal scales, but few studies have documented morphological diversity of mammalian paleocommunities on fine spatiotemporal scales in order to examine ecomorphological selectivity and ecospace filling across this critical transition. Focusing on well-sampled and temporally well-constrained mammalian faunas across the K/Pg boundary in northeastern Montana, I quantified dental-shape disparity and morphospace occupancy via landmark- and semilandmark-based geometric morphometrics and mean body size, body-size disparity, and body-size structure via body-mass estimates. My results reveal several key findings: (1) latest Cretaceous mammals, particularly metatherians and multituberculates, had a greater ecomorphological diversity than is generally appreciated, occupying regions of the morphospace that are interpreted as strict carnivory, plant-dominated omnivory, and herbivory; (2) the decline in dental-shape disparity and body-size disparity across the K/Pg boundary shows a pattern of constructive extinction selectivity against larger-bodied dietary specialists, particularly strict carnivores and taxa with plant-based diets, that suggests the kill mechanism was related to depressed primary productivity rather than a globally instantaneous event; (3) the ecomorphological recovery in the earliest Paleocene was fueled by immigrants, namely three multituberculate families (taeniolabidids, microcosmodontids, eucosmodontids) and to a lesser extent archaic ungulates; and (4) despite immediate increases in the taxonomic richness of eutherians, their much-celebrated post-K/Pg ecomorphological expansion had a slower start than is generally perceived and most likely only began 400,000 to 1 million years after the extinction event.
High Gain Antenna using Parasitic Shorted Annular Patch Structure

In this paper, the high gain and broadband antenna operating for SDMB (Satellite Digital Multimedia Broadcasting) system is proposed. The proposed antenna consists of the SAP (Shorted Annular Patch) structure, which inhibits surface-wave and the parasitic SAP element with spacing of 0.25 lambda0 in order to improve gain, bandwidth and directivity. The RHCP (Right Hand Circular Polarization) is generated by two slits, which are made along the periphery of the circular patch at the diametrically opposite points. The simulated maximum gain of the proposed antenna is 12.6 dBi, which is better 5.22(1) Hi than maximum gain of the conventional microstrip patch antenna. The measured maximum gain is 10.5 dBi. Also, the measured impedance bandwidth ( VSWR les 2 ) of the proposed antenna is 360 MHz (2.488 ~ 2.848 GHz), which is better 300 MHz than the bandwidth of the conventional microstrip patch antenna. The measured HPBW (Half Power Beam Width) of the proposed antenna is 45.8deg, and the measured FBR (Front to Back Ratio) is 15.49 dBi. The 3 dB axial ratio bandwidth is 220 MHz (2.54 ~ 2.76 GHz).
A transcriptionally active DNA-binding site for human p53 protein complexes

Recent studies have demonstrated transcriptional activation domains within the tumor suppressor protein p53, while others have described specific DNA-binding sites for p53, implying that the protein may act as a transcriptional regulatory factor. We have used a reiterative selection procedure (CASTing: cyclic amplification and selection of targets) to identify new specific binding sites for p53, using nuclear extracts from normal human fibroblasts as the source of p53 protein. The preferred consensus is the palindrome GGACATGCCCGGGCATGTCC. In vitro-translated p53 binds to this sequence only when mixed with nuclear extracts, suggesting that p53 may bind DNA after posttranslational modification or as a complex with other protein partners. When placed upstream of a reporter construct, this sequence promotes p53-dependent transcription in transient transfection assays.
Mechanisms of genotoxicity. A review of in vitro and in vivo studies with engineered nanoparticles

Abstract Engineered nanoparticles (NPs) are widely used in different technologies but their unique properties might also cause adverse health effects. In reviewing recent in vitro and in vivo genotoxicity studies we discuss potential mechanisms of genotoxicity induced by NPs. Various factors that may influence genotoxic response, including physico-chemical properties and experimental conditions, are highlighted. From 4346 articles on NP toxicity, 112 describe genotoxicity studies (94 in vitro, 22 in vivo). The most used assays are the comet assay (58 in vitro, 9 in vivo), the micronucleus assay (31 in vitro, 14 in vivo), the chromosome aberrations test (10 in vitro, 1 in vivo) and the bacterial reverse mutation assay (13 studies). We describe advantages and potential problems with different methods and suggest the need for appropriate methodologies to be used for investigation of genotoxic effects of NPs, in vitro and in vivo.
Gender Disparities in Scholarly Productivity within Academic Otolaryngology Departments

Objective To examine whether there are gender disparities in scholarly productivity within academic otolaryngology departments, as measured by academic rank and the h-index, a published, objective measure of research contributions that quantifies the number and significance of papers published by a given author. Study Design and Setting Analysis of bibliometric data of academic otolaryngologists. Methods Faculty listings from academic otolaryngology departments were used to determine academic rank and gender. The Scopus database was used to determine h-index and publication range (in years) of these faculty members. In addition, 20 randomly chosen institutions were used to compare academic otolaryngologists to faculty members in other surgical specialties. Results Mean h-indices increased through the rank of professor. Among academic otolaryngologists, men had significantly higher h-indices than women, a finding also noted on examination of faculty members from other specialties. Men had higher research productivity rates at earlier points in their career than women did. The productivity rates of women increased and equaled or surpassed those of men later in their careers. Men had higher absolute h-index values at junior academic ranks. Women academic otolaryngologists of senior rank had higher absolute h-indices than their male counterparts. Conclusions The h-index measures research significance in an objective manner and indicates that although men have higher overall research productivity in academic otolaryngology, women demonstrate a different productivity curve. Women produce less research output earlier in their careers than men do, but at senior levels, they equal or exceed the research productivity of men.
CD95/Fas induces cleavage of the GrpL/Gads adaptor and desensitization of antigen receptor signaling

The balance between cell survival and cell death is critical for normal lymphoid development. This balance is maintained by signals through lymphocyte antigen receptors and death receptors such as CD95/Fas. In some cells, ligating the B cell antigen receptor can protect the cell from apoptosis induced by CD95. Here we report that ligation of CD95 inhibits antigen receptor-mediated signaling. Pretreating CD40-stimulated tonsillar B cells with anti-CD95 abolished B cell antigen receptor-mediated calcium mobilization. Furthermore, CD95 ligation led to the caspase-dependent inhibition of antigen receptor-induced calcium mobilization and to the activation of mitogen-activated protein kinase pathways in B and T cell lines. A target of CD95-mediated caspase 3-like activity early in the apoptotic process is the adaptor protein GrpL/Gads. GrpL constitutively interacts with SLP-76 via its C-terminal SH3 domain to regulate transcription factors such as NF-AT. Cleavage of GrpL removes the C-terminal SH3 domain so that it is no longer capable of recruiting SLP-76 to the membrane. Transfection of a truncated form of GrpL into Jurkat T cells blocked T cell antigen receptor-induced activation of NF-AT. These results suggest that CD95 signaling can desensitize antigen receptors, in part via cleavage of the GrpL adaptor.
A Dilated Cardiomyopathy Revealing a Neuroblastoma: Which Link?

Acute cardiac dysfunctions associated to neuroblastoma have rarely been reported. Cases already described are mainly related to high blood pressure, and rarely to an “acute catecholamine cardiomyopathy” more frequently found in adults with pheochromocytoma or secreting paraganglioma. We here report a case of an 8-month-old infant with severe acute cardiac failure with dilated cardiomyopathy and moderate ischemic myocardial signs, revealing a favorable histoprognosis neuroblastoma. After specific treatment, evolution was favorable, and cardiac function completely recovered. The association of reversible ischemic signs with high plasmatic level of catecholamines suggests the existence of a catecholamine-induced acute cardiac dysfunction which imitates a Tako-Tsubo syndrome in neuroblastoma.
Caractéristiques phénoménologiques et fonctions perçues des pensées émotionnelles orientées vers le futur

Les principaux buts de cette etude sont d’investiguer les effets de valence sur les proprietes phenomenologiques et les fonctions percues des pensees emotionnelles orientees vers le futur - generees de facon volontaire - et de determiner si certaines proprietes permettent de predire l’intensite emotionnelle de ces pensees. Nous avons demande a 40 participants âges entre 18 et 30 ans de generer 10 pensees orientees vers le futur puis de les evaluer sur une serie de dimensions. Les resultats indiquent que les pensees positives sont plus frequentes, se manifestent avec davantage d’imagerie visuelle et sont vecues comme emotionnellement plus intenses par rapport aux pensees negatives. De plus, un modele contenant l’importance et le l’imagerie visuelle s’est avere le meilleur pour predire l’intensite des emotions attendues.
Relaxin Family Peptide Receptor (RXFP1) Coupling to Gαi3 Involves the C-Terminal Arg752 and Localization within Membrane Raft Microdomains

The relaxin family peptide receptors (RXFP) 1 and 2 are targets for the relaxin family peptides relaxin and insulin-like peptide 3 (INSL3), respectively. Although both receptors and peptides share a high degree of sequence identity, the cAMP signaling pathways activated by the two systems are quite distinct. Relaxin activation of RXFP1 initially results in accumulation of cAMP via Gαs, but this is modulated by inhibition of cAMP through GαoB. Over time, RXFP1 recruits coupling to Gαi3, causing additional cAMP accumulation via a Gαi3-Gβγ-phosphoinositide 3-kinase (PI3K)-protein kinase C (PKC)ζ pathway. In contrast, INSL3 activation of RXFP2 results in accumulation of cAMP only via Gαs, modulated by cAMP inhibition through GαoB. Thus, the aim of this study was to identify the cause of differential G-protein coupling between these highly similar receptors. Construction of chimeric receptors revealed that Gαi3 coupling is dependent upon the transmembrane region of RXFP1 and independent of the receptor ectodomain or ligand bound. Generation of C-terminal truncated receptors identified the terminal 10 amino acids of the RXFP1 C terminus as essential for Gαi3 signaling, and point mutations revealed an obligatory role for Arg752. RXFP1-mediated Gαi3, but not Gαs or GαoB, signaling was also found to be dependent upon membrane rafts, and RXFP1 coupled to Gαi3 after only 3 min of receptor stimulation. Therefore, RXFP1 coupling to the Gαi3-Gβγ-PI3K-PKCζ pathway requires the terminal 10 amino acids of the RXFP1 C terminus and membrane raft localization, and the observed delay in this pathway occurs downstream of Gαi3.
A Manganese Superoxide Dismutase (SOD2)-Mediated Adaptive Response

Very low doses of ionizing radiation, 5 to 100 mGy, can induce adaptive responses characterized by elevation in cell survival and reduction in micronuclei formation. Utilizing these end points, RKO human colon carcinoma and transformed mouse embryo fibroblasts (MEF), wild-type or knockout cells missing TNF receptors 1 and 2 (TNFR1–R2–), and C57BL/6 and TNFR1–R2– knockout mice, we demonstrate that intact TNF signaling is required for induction of elevated manganese superoxide dismutase (SOD2) activity (P < 0.001) and the subsequent expression of these SOD2-mediated adaptive responses when cells are challenged at a later time with 2 Gy. In contrast, amifostine's free thiol form WR1065 can directly activate NF-κB giving rise to elevated SOD2 activity 24 h later and induce an adaptive response in both MEF wild-type and TNF signaling defective TNFR1–R2– cells. Transfection of cells with SOD2 siRNA completely abolishes both the elevation in SOD2 activity and expression of the adaptive responses. These results were confirmed in vivo using a micronucleus assay in splenocytes derived from C57BL/6 and TNFR1–R2– knockout mice that were exposed to 100 mGy or 400 mg/kg amifostine 24 h prior to exposure to a 2 Gy whole-body dose. A dose of 100 mGy also conferred enhanced protection to C57BL/6 mice exposed 24 h later to 100 mg/kg of N-Ethyl-N-nitrosourea (ENU). While very low radiation doses require an intact TNF signaling process to induce a SOD2-mediated adaptive response, amifostine can induce a similar adaptive response in both TNF receptor competent and knockout cells, respectively.
What can be seen in a glance ?

____________________________________________________________________________________________________ * This work was supported by NIMH Grant R01-MH58606. Correspondence concerning this article should be either author at: Department of Psychology, 1 University Station, A8000, The University of Texas at Austin, Austin, Texas 78712. Electronic mail may be sent to t.thornton@mail.utexas. edu, gilden@psy.utexas. edu What can be seen in a glance?
Photodynamic therapy of multiple nonmelanoma skin cancers with verteporfin and red light-emitting diodes: two-year results evaluating tumor response and cosmetic outcomes.

BACKGROUND Efficient treatment of patients with multiple synchronous nonmelanoma skin cancers represents a therapeutic challenge. OBJECTIVE To study the safety and efficacy of photodynamic therapy (PDT) with verteporfin and red light in the treatment of multiple nonmelanoma skin cancers. DESIGN Open-label, randomized, multicenter, dose-ranging phase 2 study conducted at 4 North American university-based dermatology clinics. PATIENTS Fifty-four patients with 421 multiple nonmelanoma skin cancers including superficial and nodular basal cell carcinoma and squamous cell carcinoma in situ (Bowen disease). METHODS A single intravenous infusion of 14 mg/m(2) of verteporfin followed 1 to 3 hours later by exposure of tumors to 60, 120, or 180 J/cm(2) of red light (688 +/- 10 nm) from a light-emitting diode panel. MAIN OUTCOME MEASURES Pathologic response of treated sites was assessed at 6 months. Clinical and cosmetic responses were assessed and graded at 6 weeks, 3 months, and 6 months after verteporfin PDT, with optional follow-up visits at 12, 18, and 24 months. RESULTS The histopathologic response, defined as absence of tumor on biopsy specimens 6 months after verteporfin PDT, ranged from 69% at 60 J/cm(2) to 93% at 180 J/cm(2). At 24 months of follow-up (276 tumors in 31 patients), the clinical complete response rate ranged from 51% at 60 J/cm(2) to 95% at 180 J/cm(2). No significant systemic adverse events were observed; most events occurred at the treated tumor sites and included events such as pain. Overall, 65% (95% confidence interval, 58%-71%) of tumors were judged to have good to excellent cosmesis at 24 months. CONCLUSION A single course of verteporfin PDT showed treatment benefit for patients with multiple nonmelanoma skin cancers.
Long-term clinical and magnetic resonance imaging follow-up assessment of patients with lumbar spinal stenosis after laminectomy.

STUDY DESIGN A cross-sectional retrospective study to observe the correlation between postoperation findings shown on magnetic resonance imaging and clinical observations of 56 patients 10 years after laminectomy for lumbar spinal stenosis. OBJECTIVE To evaluate the relation between postoperation findings on magnetic resonance imaging and surgical outcome in patients surgically treated for lumbar spinal stenosis. SUMMARY OF BACKGROUND DATA Surgical management of lumbar spinal stenosis is based on the compression seen in radiologic imaging of neurovascular structures in the vertebral canal, but the success of surgical decompression and its correlation with clinical observations very seldom have been monitored by postoperation radiologic imaging. METHODS In this study, 56 patients surgically treated for lumbar spinal stenosis were re-examined clinically by use of the Oswestry disability questionnaire. Their walking capacity was evaluated by the treadmill test. Severity of pain before and after the treadmill test was investigated using a visual analog scale. Patients' perception of improvement measured as the change in their condition during the preceding 5 years was elicited by a questionnaire. On the basis of the stenotic findings on magnetic resonance imaging, the patients were classified into no stenosis (NoSten, n = 15) and stenosis (Sten, n = 41) groups, and a summative degenerative scale also was constructed with the findings categorized as follows: disc degeneration, disc herniation, facet joint arthrosis, and degenerative spondylolisthesis. RESULTS Whereas the patients' perception of improvement correlated very strongly with the Oswestry score and walking capacity, there was no statistical difference between the NoSten and Sten groups in the Oswestry score, walking capacity, perception of improvement, or severity of pain. The effect of the summative degenerative scale on the patients' walking capacity was 13 times greater than the effect of the minimum area of the dural sac. CONCLUSIONS Patients' perception of improvement had a much stronger correlation with long-term surgical outcome than structural findings seen on postoperation magnetic resonance imaging. Moreover, degenerative findings had a greater effect on patients' walking capacity than stenotic findings.
Trust-distrust protocol for the secure routing in wireless sensor networks

Now a days usage of Wireless Sensor Networks (WSNs) is increasing, because of its wide application. Unlike common networks the WSNs have the capability of reconfiguration, whenever any defect occurs in the network. However, while routing in these network the loss of data is occurring due to its security lack. Hence many researchers have presented their research for providing secure routing in WSNs. The security is still an issue in routing of WSNs. In this paper, we have developed a novel protocol for the secure routing of WSNs, and named as Trust-Distrust Protocol (TDP). The proposed protocol has four stages, initial stage is topology management, where an improved k-means algorithm is applied. Then the second stage is Link Quality Appraisal, which means fitness evaluation of every nodes in the network. The third stage is Grading, in which based on the fitness value a grade point is allotted to every node. In the last stage the secure path for the routing is determined based on grade point. The proposed TDP is tested in NS2 and the performance is compared with the existing LEACH protocol. Ultimately the proposed protocol outperform the performance of the existing routing protocol.
Metaphor or Simile

CCSS. RL.3. 4 |© http://www.englishworksheetsland. com Metaphor | Simile Figurative language uses images and comparisons to describe things. A metaphor is figurative language. Another kind of figurative language is called a simile. A simile is like a metaphor, except that a simile uses the words “like” or “as” to compare one thing to another. “Frank is Marcia’s satellite” is a metaphor. “Frank hangs around Marcia like a satellite” is a simile. Directions: Rewrite the sentences below, adding a simile to make the meaning more clear. Remember, a simile uses the words “like” or “as” to compare one thing to another. Use the pictures for inspiration!
Domain mining for machine translation

Massive amounts of data for data mining consist of natural language data. A challenge in natural language is to translate the data into a particular language. Machine translation can do the translation automatically. However, the models trained on data from a domain tend to perform poorly for different domains. One way to resolve this issue is to train domain adaptation translation and language models. In this work, we use visualizations to analyze the similarities of domains and explore domain detection methods by using text clustering and domain language models to discover the domain of the test data. Furthermore, we present domain adaptation language models based on tunable discounting mechanism and domain interpolation. A cross-domain evaluation of the language models is performed based on perplexity, in which considerable improvements are obtained. The performance of the domain adaptation models are also evaluated in Chinese-to-English machine translation tasks. The experimental BLEU scores indicate that the domain adaptation system significantly outperforms the baseline especially in domain adaptation scenarios.