Miracle-dz/UniFAR-FTUs huggingface dataset:
Glutamate receptor agonists increase the expression of Fos, Fra, and AP‐1 DNA binding activity in the mammalian brain

Administration of convulsant doses of Metrazole (pentylenetetrazol) and picrotoxin, as well as maximal electroshock, results in a rapid but transient increase in c‐fos mRNA in mouse brain. Elevation of c‐fos mRNA is followed by the accumulation and subsequent disappearance of Fos, the protein encoded by c‐fos. In addition, immunoblots reveal the induction of two additional proteins that are antigenically related to Fos (Fra, Fos‐related antigens). Fos and the various Fra appear and disappear in a staggered manner over an 8 hour period, such that at longer times after stimulation the brain contains no Fos but relatively large amounts of Fra (the latter being designated here by their apparent molecular weights, Fra‐46K and Fra‐35K). Previous studies have established that Fos, as well as several Fra, contribute to transcription factor AP‐1 nucleoprotein complexes along with Jun, the product of the jun proto‐oncogene. The appearance in brain of Fos and Fra coincides with a protracted increase in total AP‐1 DNA binding activity, indicating that all the Fos‐like proteins can participate in AP‐1 complexes. Furthermore, the molecular composition of these complexes alters with time after stimulation. The induction of c‐fos by Metrazole is blocked or attenuated by known anticonvulsants such as diazepam and valproate as well as the N‐methyl‐D‐aspartate (NMDA) receptor antagonists, 2‐amino‐5‐phosphonovaleric acid (APV) and MK‐801. This suggests that fos induction might involve stimulation of a glutamate receptor. This conclusion was strengthened by the observations that two glutamate receptor agonists, kainic acid and NMDA, induced c‐fos expression. The induction of c‐fos by NMDA had a similar kinetic and pharmacological profile to that of Metrazole. Kainic acid, in contrast, caused a protracted induction of c‐fos not seen in any of the other paradigms. Therefore, it is likely that both the kainate and NMDA forms of the glutamate receptor may participate independently in the induction of c‐fos in the rodent nervous system.
Extended state based H∞ filter

This paper considers the filtering problem for a class of nonlinear uncertain systems with process and measurement noise. An extended state based H∞ filter, with the idea of timely estimating the unknown dynamics, is proposed for better robustness and higher estimation precision. We prove the stability of the proposed filter for a class of nonlinear uncertain systems with the initial estimation error, the uncertain dynamics and the noises being not required to be small enough. Moreover, both the augmented cost function and the original cost function are proved to be upper bounded by the desired bound so that the robustness against the disturbance is guaranteed. The simulation results validate the effectiveness of the proposed filter.
α2 Adrenergic Receptor Subtypes Expressed in Chinese Hamster Ovary Cells Activate Differentially Mitogen-activated Protein Kinase by a p21ras Independent Pathway (*)

Epinephrine stimulation of rat α2D, α2B, and α2X adrenergic receptor subtypes, expressed stably in Chinese hamster ovary (CHO) cells, caused a rapid, transient activation of mitogen-activated protein kinase (MAPK), with subtype-specific different efficiencies. The order of activation was CHO-2B ∼ CHO-2D ≫ CHO-2C. Pertussis toxin blocked the stimulation of MAPK enzymatic activity and the parallel MAPK phosphorylation, demonstrating that these responses are mediated by pertussis toxin-sensitive Gi proteins. Contrary to what has been reported for the α2A subtype expressed in rat-1 fibroblasts, epinephrine did not cause any detectable activation of p21ras in the CHO transfectants. Furthermore, combined application of epinephrine and phorbol myristate acetate had a potent cooperative but not additive effect in clones CHO-2D and CHO-2B but not in CHO-2C, suggesting that protein kinase C is probably differently involved in the signaling by the three α2 receptor subtypes. These results show that in CHO cells, the different α2 adrenergic receptor subtypes utilize differential pathways to activate MAPK in a p21ras-independent way.
The evolution of mathematical immunology

Summary: The types of mathematical models used in immunology and their scope have changed drastically in the past 10 years. Classical models were based on ordinary differential equations (ODEs), difference equations, and cellular automata. These models focused on the ‘simple’ dynamics obtained between a small number of reagent types (e.g. one type of receptor and one type of antigen or two T‐cell populations). With the advent of high‐throughput methods, genomic data, and unlimited computing power, immunological modeling shifted toward the informatics side. Many current applications of mathematical models in immunology are now focused around the concepts of high‐throughput measurements and system immunology (immunomics), as well as the bioinformatics analysis of molecular immunology. The types of models have shifted from mainly ODEs of simple systems to the extensive use of Monte Carlo simulations. The transition to a more molecular and more computer‐based attitude is similar to the one occurring over all the fields of complex systems analysis. An interesting additional aspect in theoretical immunology is the transition from an extreme focus on the adaptive immune system (that was considered more interesting from a theoretical point of view) to a more balanced focus taking into account the innate immune system also. We here review the origin and evolution of mathematical modeling in immunology and the contribution of such models to many important immunological concepts.
Regulation of the Fibroblast Growth Factor Receptor 3 Promoter and Intron I Enhancer by Sp1 Family Transcription Factors*

Fibroblast growth factor receptor 3 (FGFR3) has a complex spatial and temporal pattern of expression and is essential for the normal development of a diverse set of tissues. Recently, mutations have been identified in FGFR3 that result in constitutive tyrosine kinase activity and cause a number of different human skeletal disorders. To examine the regulatory mechanisms governing FGFR3 expression, the promoter for the FGFR3 gene was identified and characterized. It resides in a CpG island, which encompasses the 5′ end of the FGFR3 gene and lacks classical cis-regulatory motifs. As little as 100 base pairs of sequence 5′ to the initiation site can confer a 20–40-fold increase in transcriptional activity upon a promoter-less vector. The transcriptional activity of thesecis-regulatory sequences is further stimulated by elements found within the first intron. Mapping of the enhancer activity found within intron I identified two purine-rich sequence motifs between +340 and +395. Electrophoretic mobility shift assays demonstrated that sequences within this region bind members of the Sp1 family of transcription factors. In a background lacking Sp1-like activity, we demonstrate that Sp1 can enhance transcription of the minimal promoter (which contains five classical Sp1 sites), whereas both Sp1 and Sp3 can enhance transcription through the elements found in intron I. Although these transcription factors are ubiquitously expressed, we demonstrate that the sequences between −220 and +609 of the FGFR3 gene are sufficient to promote the tissue-specific expression of a reporter gene in transgenic mice.
Vision restoration therapy (VRT) efficacy as assessed by comparative perimetric analysis and subjective questionnaires.

PURPOSE We wished to evaluate the efficacy of vision restoration therapy (VRT) in patients with post-chiasmatic brain damage using different functional perimetric tests. These were compared with measures of subjective vision and reaction time. METHODS An open trial was conducted with hemianopia/scotoma (n=16) patients. Before and after 6 months of VRT results of high resolution (HRP) and Tuebingen automated perimetry (TAP) were evaluated and compared to performance in a Scanning Laser Ophthalmoscope (SLO) as previously reported. Whereas TAP and HRP used above-threshold or near-threshold individual target stimuli on grey background, the SLO used a psychophysical task of detection of three black targets (reverse stimulus) on bright red, patterned background. Subjective testimonials of activities of daily living (ADL) were probed with questionnaires and interviews. RESULTS Before VRT, the visual field border as assessed by SLO was located significantly closer to the vertical midline than the HRP and TAP border (border mismatch). After VRT the SLO border was still unchanged whereas HRP measurements revealed significant border shifts due to improved stimulus detection (p<0.0001) and improved reaction time (p<0.005) . Fewer misses were also observed in both eyes with TAP (p<0.01) which was primarily due to a significant shift of the absolute borders. Thus, VRT potentiated the mismatch between the SLO borders and the HRP/TAP borders. Fixation performance and the blind spot position remained unchanged after VRT. ADL ratings in the questionnaire improved significantly after VRT which was confirmed by independent patient testimonials. CONCLUSIONS We replicated earlier findings that VRT improves stimulus detection in HRP and TAP perimetry which were accompanied by subjective, visual improvements. These changes are not caused by fixation or eye movement artifacts. Because the SLO border was located significantly closer to the vertical midline before VRT ("border mismatch") and, in contrast to HRP and TAP, did not change after VRT, we interpret this border mismatch to indicate that the SLO task was too difficult to perform and thus insensitive to VRT effects. Significant reaction time improvements indicate that plasticity of temporal processing might play an important role in vision restoration after brain damage. A further description of the precise psychophysical nature of the restored areas of residual vision is now warranted.
The proteomic analysis improved by cleavage kinetics‐based fractionation of tryptic peptides

Selective enrichment of specific peptides is an effective way to identify low abundance proteins. Fractionation of peptides prior to mass spectrometry is another widely used approach to reduce sample complexity in order to improve proteome coverage.In this study, we designed a multi‐stage digestion strategy to generate peptides with different trypsin cleavage kinetics. It was found that each of the collected peptide fractions yielded many new protein identifications compared to the control group due to the reduced complexity. The overlapping peptides identified between adjacent fractions were very low, indicating that each fraction had different sets of peptides. The multi‐stage digestion strategy separates tryptic peptides with different cleavage kinetics while RPLC separates peptides with different hydrophobicity. These two separation strategies were highly orthogonal, and showed an effective multidimensional separation to improve proteome coverage.
Model-based telehaptic systems with time varying communication delay

In this paper, we propose model-based control design strategy for the trajectory tracking of the internet-based bilateral telehaptic systems. The communication time delay between local-master and remote-slave platform is assumed to be symmetrical and unsymmetrical nature. The design comprises delayed position signals with the local velocity signals and the known structure of the master and slave system dynamics. Using Lyapunov-Krasovskii-like functional, asymptotic tracking property of the position and velocity of the master-slave closed-loop systems with symmetric and unsymmetric time varying communication delays are developed. Finally, simulations are conducted to demonstrate the validity of the proposed design for real-time telehaptic operation.
Transcription of the mouse ribosomal spacer region

This paper describes experiments designed to test the hypothesis that DNA sequences upstream from the mouse rRNA promoter are transcribed in vivo or in vitro. Plasmid pB28 contains a SalI restriction fragment that extends from -169 to -1,894 base pairs, with respect to the origin of transcription of pre-rRNA. Labeled RNA synthesized in intact cells does not hybridize to this region. Neither S1 nuclease mapping nor RNA dot blot hybridization revealed the presence of sequences complementary to this region. Transcriptional studies carried out in vitro indicated that this region is not transcribed under conditions that are optimal for utilization of the authentic rRNA promoter. Moreover, this region does not appear to form stable transcription complexes with RNA polymerase I transcription components. These data indicate that the mouse rDNA repeating unit differs from those of Xenopus spp. and Drosophila melanogaster in that reduplicated RNA polymerase I promoters are not found in the mouse rDNA spacer region.
Monte Carlo simulation of the statistical uncertainty of emission measurements in an ideal reverberation chamber

This paper describes the results of a Monte Carlo simulation to quantify the statistical uncertainty of emission measurements in the scope of electromagnetic compatibility in a reverberation chamber. Such a measurement can be performed based on the average or maximum received power at the reference antenna. Depending on whether value is measured, different parameters as the chamber validation factor CVF, the chamber loading factor CLF or the insertion loss IL are needed to calculate the total radiated power of a device under test. Each parameter as well as the measurement itself features its own statistical uncertainty, which are combined into a joint statistical uncertainty of the total radiated power, which is analyzed in this paper.
Association of BRAFV600E mutation with clinicopathological features of papillary thyroid carcinoma: a study on a Chinese population.

BACKGROUND The new finding of the heterogeneous distribution of BRAF(V600E) mutation in primary papillary thyroid carcinoma suggested the percentage of BRAF(V600E) alleles should be taken into consideration when evaluating its association with clinicopathological features of papillary thyroid carcinoma. The aim of this study was to detect both the presence and the percentage of BRAF(V600E) alleles in fine-needle aspiration biopsy samples and to assess its association with clinicopathological characteristics of papillary thyroid carcinoma in a Chinese population. MATERIALS AND METHODS Fine needle aspiration samples were collected in a total of 182 patients (132 conventional papillary thyroid carcinomas and 50 goiters). The associations of the presence and percentage of BRAF(V600E) alleles genotyped by pyrosequencing with clinicopathological characteristics were evaluated in papillary thyroid carcinomas. RESULTS 80 (60.61%) of papillary thyroid carcinomas exhibited BRAF(V600E) mutation in a range of 7.7% to 46.3% of the total BRAF alleles. The presence of BRAF(V600E) mutation was significantly associated with extrathyroidal invasion. There was no significant difference between the presence of BRAF(V600E) mutation and other clinicopathological features. It was not found that the significant relationship between percentage of BRAF(V600E) alleles and clinicopathological characteristics. CONCLUSION We concluded that the presence of BRAF(V600E) could be preoperatively predictive of extrathyroidal invasion in a Chinese population.
Blind collision multiplicity detection for wireless access with retransmission diversity

Multiple access protocols with retransmission diversity resolve packet collisions through source separation techniques. The number of retransmissions to achieve the necessary diversity level equals the collision multiplicity, whose proper detection is essential for good performance. The well-known network-assisted diversity multiple access employs the rank test method to detect the multiplicity blindly, but constant channel parameters throughout the retransmissions and the tight control of the transmitter phase are required. In this paper, a superior blind collision multiplicity detection technique is introduced for per-slot varying channels by combining the minimum description length (MDL) criterion and the rank test method. The proposed method and the rank test are compared both theoretically and experimentally.
Topoisomerase I Requirement for Death Receptor-induced Apoptotic Nuclear Fission*

Topoisomerase I (Top1) is known to relax DNA supercoiling generated by transcription, replication, and chromatin remodeling. However, it can be trapped on DNA as cleavage complexes (Top1cc) by oxidative and carcinogenic DNA lesions, base damage, and camptothecin treatment. We show here that Top1 is also functionally involved in death receptor-induced programmed cell death. In cells exposed to TRAIL or Fas ligand, Top1cc form at the onset of apoptosis. Those apoptotic Top1cc are prevented by caspase inhibition and Bax inactivation, indicating that both caspases and the mitochondrial death pathway are required for their formation. Accordingly, direct activation of the mitochondrial pathway by BH3 mimetic molecules induces apoptotic Top1cc. We also show that TRAIL-induced apoptotic Top1cc are preferentially formed by caspase-3-cleaved Top1 at sites of oxidative DNA lesions with an average of one apoptotic Top1cc/100 kbp. Examination of Top1 knock-down cells treated with TRAIL revealed similar DNA fragmentation but a marked decrease in apoptotic nuclear fission with reduced formation of nuclear bodies. Thus, we propose that Top1 contributes to the full apoptotic responses induced by TRAIL.
Fuzzy Sliding-Mode Control of Active Suspensions

In this paper, a robust fuzzy sliding-mode controller for active suspensions of a nonlinear half-car model is introduced. First, a nonchattering sliding-mode control is presented. Then, this control method is combined with a single-input-single-output fuzzy logic controller to improve its performance. The negative value of the ratio between the derivative of error and error is the input and the slope constant of the sliding surface of the nonchattering sliding-mode controller is the output of the fuzzy logic controller. Afterwards, a four-degree-of-freedom nonlinear half-car model, which allows wheel hops and includes a suspension system with nonlinear spring and piecewise linear damper with dry friction, is presented. The designed controllers are applied to this model in order to evaluate their performances. It has been shown that the designed controller does not cause any problem in suspension working limits. The robustness of the proposed controller is also investigated for different vehicle parameters. The results indicate the success of the proposed fuzzy sliding-mode controller.
Patients Operated On for Initially Unresectable Colorectal Liver Metastases With Missing Metastases Experience a Favorable Long-Term Outcome

Background:After chemotherapy, complete clinical responses of colorectal liver metastases (CRLMs) increasingly occur, but these responses are rarely complete pathological responses. The management of patients with missing metastases, that is, CRLMs that disappear under chemotherapy are undetectable intraoperatively and finally left in place, continues to be controversial. The aim of this study was to assess the long-term outcome of patients with “missing CRLMs. ” Patients:Between 1999 and 2007, among 523 patients operated on for CRLMs, 96 missing CRLMs were observed and left in place in 27 originally unresectable patients. All of these patients received preoperative chemotherapy. Hepatic arterial infusion (HAI) of oxaliplatin combined with systemic 5-fluorouracil was administered in 23 patients, including 12 before hepatectomy and 11 after. Hepatic surgery was performed after a minimal interval of 3 months during which CRLMs had disappeared on imaging. Results:After a median follow-up of 55 months (24–137) after hepatic surgery, an intrahepatic recurrence was diagnosed in 14 (52%) patients, but the recurrence rate was significantly lower in patients who had received adjuvant HAI compared with the others (27% vs 83%, P = 0.006). Recurrences arose at the site of the missing CRLMs in 9 (33%) patients, but was associated in all cases with another recurrence in the liver. The 5-year overall survival rate of these 27 highly chemosensitive patients was 80%, and the 5-year disease-free survival rate was 23%. Conclusion:Highly chemosensitive patients, whose initially unresectable CRLMs become resectable because of missing CRLMs left in place, have a favorable long-term outcome. Missing CRLMs should not be longer, a contraindication to hepatic surgery. Use of postoperative HAI of oxaliplatin can help to reduce the risk of hepatic relapse.
Suppression of sporulation of Botrytis cinerea by antagonists applied after infection

The ability of the antagonists Epicoccum nigrum, Gliocladium roseum and Trichoderma harzianum to reduce sporulation of Botrytis cinerea when applied after infection was investigated in bean-leaf-disc assays under a variety of environmental conditions. G. roseum significantly reduced sporulation of B. cinerea when applied up to 120 h after the pathogen, whereas E. nigrum and T. harzianum suppressed sporulation when applied up to 72 h after infection. When applied 48 h after infection, all antagonists reduced sporulation of B. cinerea at temperatures of 15–25°C. G. roseum was highly effective at reducing sporulation of B. cinerea throughout this temperature range, but not at 10°C, whereas E. nigrum and T. harzianum showed their greatest relative effects on sporulation at 25°C. Antagonism by G. roseum was favoured by relative humidity of 98%, while the effect of relative humidity on E. nigrum and T. harzianum was equivocal. Under the conditions of the assay system, antagonist concentration did not have a consistent effect on reduction of sporulation.
Focus on ceftazidime-avibactam for optimizing outcomes in complicated intra-abdominal and urinary tract infections

Introduction: Complicated intra-abdominal infections and urinary tract infections are frequently associated with Gram-negative bacteria and treatment can be hampered by the involvement of resistant organisms. A common resistance mechanism is β-lactamase production which confers resistance to β-lactam antibiotics. Areas covered: This article summarizes β-lactamases found among Gram-negative bacteria as well as providing an overview of complicated intra-abdominal infections and urinary tract infections and the impact inappropriate antibiotic therapy and antibiotic resistance has in their treatment. The author reviews the activity of ceftazidime-avibactam, including animal model data and microbiological data from Phase II clinical trials. This article also highlights Phase III clinical trials of ceftazidime-avibactam that are ongoing or completed and briefly discusses other β-lactamase inhibitor combinations currently in development. Expert opinion: The increasing problem and complexity of β-lactamase resistance has been met by resurgence in the development of β-lactamase inhibitor combinations. These show promise in the treatment of resistant infections. One β-lactamase inhibitor in advanced development with a broad spectrum of activity is avibactam, covering class A, class C and some class D enzymes. Importantly, the activity of avibactam also includes carbapenemases such as the KPC and OXA-48. The combination of avibactam with the cephalosporin ceftazidime is attractive, given the spectrum of antimicrobial activity and the low toxicity of the cephalosporin class.