Miracle-dz/UniFAR-FTUs huggingface dataset:
Pre‐synaptic GABAB receptors inhibit glutamate release through GIRK channels in rat cerebral cortex

Neuronal G protein‐gated inwardly rectifying potassium (GIRK) channels mediate the slow inhibitory effects of many neurotransmitters post‐synaptically. However, no evidence exists that supports that GIRK channels play any role in the inhibition of glutamate release by GABAB receptors. In this study, we show for the first time that GABAB receptors operate through two mechanisms in nerve terminals from the cerebral cortex. As shown previously, GABAB receptors reduces glutamate release and the Ca2+ influx mediated by N‐type Ca2+ channels in a mode insensitive to the GIRK channel blocker tertiapin‐Q and consistent with direct inhibition of this voltage‐gated Ca2+ channel. However, by means of weak stimulation protocols, we reveal that GABAB receptors also reduce glutamate release mediated by P/Q‐type Ca2+ channels, and that these responses are reversed by the GIRK channel blocker tertiapin‐Q. Consistent with the functional interaction between GABAB receptors and GIRK channels at nerve terminals we demonstrate by immunogold electron immunohistochemistry that pre‐synaptic boutons of asymmetric synapses co‐express GABAB receptors and GIRK channels, thus suggesting that the functional interaction of these two proteins, found at the post‐synaptic level, also occurs at glutamatergic nerve terminals.
THE BUSINESS MODEL PATTERN DATABASE — A TOOL FOR SYSTEMATIC BUSINESS MODEL INNOVATION

Companies are more frequently seen shifting their focus from technological innovation towards business model innovation. One efficient option for business model innovation is to learn from existing solutions, i.e., business model patterns. However, the various understandings of the business model pattern concept are often confusing and contradictory, with the available collections incomplete, overlapping, and inconsistently structured. Therefore, the rich body of literature on business model patterns has not yet reached its full potential for both practical application as well as theoretic advancement. To help remedy this, we conduct an exhaustive review, filter for duplicates, and structure the patterns along several dimensions by applying a rigorous taxonomy-building approach. The resulting business model pattern database allows for navigation to the relevant set of patterns for a specific impact on a company’s business model. It can be used for systematic business model innovation, which we illustrate via a simplified case study.
Low Thymidylate Synthase Expression in the Primary Tumor Predicts Favorable Clinical Outcome in Resected Gastric Cancer Patients Treated with Adjuvant Tegafur

Objective: To assess the thymidylate synthase protein (TS) in tumor cells of resected gastric cancer patients treated with adjuvant tegafur (TG), we reviewed the outcome of 94 randomized patients treated either with adjuvant TG plus mitomycin C (MMC) or MMC alone. Methods: TS was determined in 76 out of 94 patients, previously randomized to receive adjuvant TG, 500 mg/m2/day p.o. for 6 months plus four courses of MMC, 10– 20 mg/m2 i.v. every 6 weeks or MMC alone. An immunohistochemical assessment with the monoclonal antibody TS-106 was performed. Results: Low TS was observed in 38 patients (20 treated with TG-MMC and 18 with MMC) and high TS in the other 38 patients (21 treated with TG-MMC and 17 with MMC). After 10 years’ median follow-up time, 61% of adjuvant TG-MMC patients and 43% of MMC patients were alive and disease-free. Disease-free survival and overall survival were significantly better for patients treated with TG-MMC compared to MMC adjuvant (p = 0.0277 and p = 0.05), and low-TS compared to high-TS patients (p = 0.0184 and p = 0.0198). In 38 low-TS patients we observed an 83% chance to be disease-free in TG-MMC-treated patients and 55% in MMC-treated patients (p = 0.04). Conclusions: A low TS level determines a subset of patients that may benefit from adjuvant oral TG when added to MMC showing a 5-year cure rate of more than 80%.
Effects of early pregnancy loss on hormone levels in the subsequent menstrual cycle

Previous studies of hormone patterns after clinical miscarriage suggest reduced pituitary function. Hormonal effects of very early pregnancy loss (before 6 weeks gestation) have not been described. We used within-woman differences between menstrual cycles in urinary hormone measurements from women in the North Carolina Early Pregnancy Study to describe hormonal changes after very early pregnancy loss (n = 28 early losses; 80 non-conception comparison cycles). We found lower pre-ovulatory luteinising hormone and shorter luteal phase length after very early pregnancy loss, but the differences were non-significant (p > 0.3) and smaller than those reported in the spontaneous miscarriage literature. Consistent with the reduced pituitary function reported post-spontaneous miscarriage, we found a slower rate of oestrogen rise (p = 0.08). There was no evidence of lower mid-luteal steroid levels as has been suggested for post-spontaneous miscarriage cycles. Very early pregnancy losses do not appear to influence subsequent menstrual cycles to the same degree as spontaneous miscarriages.
Validating a Pragmatic Approach to Cognitive Screening in Stroke Prevention Clinics Using the Montreal Cognitive Assessment

Background and Purpose— The Montreal Cognitive Assessment (MoCA) is used commonly to identify cognitive impairment (CI), but there are multiple published cut points for normal and abnormal. We seek to validate a pragmatic approach to screening for moderate–severe CI, by classifying patients into high-, intermediate-, and low-risk categories. Methods— A total of 390 participants attending an academic Stroke Prevention Clinic completed the MoCA and more detailed neuropsychological testing. Between April 23, 2012 and April 30, 2014, all consecutive new referrals to the regional Stroke Prevention Clinic who were English-speaking, not severely aphasic, and could see and write well enough to complete neuropsychological testing were assessed for inclusion, and consenting patients were enrolled. CI was defined as ≥2 SDs below normal for age and education on at least 2 cognitive subtests. A single cut point for CI was compared with 2 cut points (high sensitivity and high specificity) generated using receiver operator characteristic and area under the curve analyses. The intermediate-risk group contained those scoring between the 2 cut points. Results— Thirty-four percent of participants had a symptomatic or silent stroke, 34% were seen for possible or probable transient ischemic attack, and 32% were diagnosed with other vascular or nonvascular conditions. Using a single cut point, sensitivity and specificity were optimal with MoCA ⩽22, (sensitivity=60.4%, specificity=89.9%, area under the curve=0.801, positive predictive value=48.5%, negative predictive value=93.5%, positive likelihood ratio=6, and negative likelihood ratio=0.4). Using 2 cut points, sensitivity was optimal with MoCA ≥28 (sensitivity=96.2%, negative predictive value =97.6%, and negative likelihood ratio=1.27), and specificity was optimal with MoCA ⩽22 (specificity=89.9%, positive predictive value=48.5%, and positive likelihood ratio=6). Conclusions— Stratifying participants into 3 categories facilitates the identification of a homogenous group at low risk for CI, as well as 2 other groups with intermediate and higher risk. This approach could facilitate clinical care pathways and patient selection for research.
Adhesion- and stress-related adaptation of glioma radiochemoresistance is circumvented by β1 integrin/JNK co-targeting

Resistance of cancer stem-like and cancer tumor bulk cells to radiochemotherapy and destructive infiltration of the brain fundamentally influence the treatment efficiency to cure of patients suffering from Glioblastoma (GBM). The interplay of adhesion and stress-related signaling and activation of bypass cascades that counteract therapeutic approaches remain to be identified in GBM cells. We here show that combined inhibition of the adhesion receptor β1 integrin and the stress-mediator c-Jun N-terminal kinase (JNK) induces radiosensitization and blocks invasion in stem-like and patient-derived GBM cultures as well as in GBM cell lines. In vivo, this treatment approach not only significantly delays tumor growth but also increases median survival of orthotopic, radiochemotherapy-treated GBM mice. Both, in vitro and in vivo, effects seen with β1 integrin/JNK co-inhibition are superior to the monotherapy. Mechanistically, the in vitro radiosensitization provoked by β1 integrin/JNK targeting is caused by defective DNA repair associated with chromatin changes, enhanced ATM phosphorylation and prolonged G2/M cell cycle arrest. Our findings identify a β1 integrin/JNK co-dependent bypass signaling for GBM therapy resistance, which might be therapeutically exploitable.
EVALUATION OF A NEW SET OF REAL-TIME PCR FOR BRUCELLA DETECTION WITHIN HUMAN AND ANIMAL SAMPLES

A quantitative TaqMn Real-Time PCR assay was developed and its diagnostic value on human serum and livestock samples were evaluated. Brucella species could be distributed through communities as a biological agent. Rapid detection of biological threat agents is critical for timely therapeutic administration. Quantitative real-time PCR provides a rapid, sensitive and specific tool for molecular identification of this agent. We evaluated a new real-time PCR set by numerous human and livestock samples. For primers and probe designation BCSP31 of B. melitensis 16 M was used. Different sero-positive human samples and tissue samples livestock with suspected brucellosis were then assayed after primary adaptation of Q-PCR in the laboratory. The detection limit of the assay was 10 fg (equivalent to 2 genome). Totally 50 samples (25 sero-positive, 25 sero-negative) of patients and 75 samples from slaughtered livestock (due to brucellosis) were collected and assayed by Q-PCR, along with control samples. Brucella genome were detected by this real-time set from nearly 42% (5 out of 12) of negative samples by conventional PCR. This system also detected brucella contamination in 46 out of 75 animal samples.
Labor and Delivery Complications among Teenage Mothers

A broad set of academic literatures shows that childbearing is associated with a variety of negative health outcomes for teenage mothers. Many researchers question whether teenage childbearing is the causal explanation for the negative outcomes (i.e., whether there is a biological effect of teenage childbearing or whether the relationship is due to other factors correlated with health and teenage childbearing). This study investigates the relationship between teenage childbearing and labor and delivery complications using a panel of confidential birth certificate data over the period from 1994 to 2003 from the state of Texas. Findings show that compared to mothers aged 25 to 29 having their first child, teenager mothers appear to have superior health in most—but not all—labor and delivery outcomes.
Living in flowing water increases resistance to ultraviolet B radiation

ABSTRACT Ultraviolet B radiation (UV-B) is an important environmental driver that can affect locomotor performance negatively by inducing production of reactive oxygen species (ROS). Prolonged regular exercise increases antioxidant activities, which may alleviate the negative effects of UV-B-induced ROS. Animals naturally performing exercise, such as humans performing regular exercise or fish living in flowing water, may therefore be more resilient to the negative effects of UV-B. We tested this hypothesis in a fully factorial experiment, where we exposed mosquitofish (Gambusia holbrooki) to UV-B and control (no UV-B) conditions in flowing and still water. We show that fish exposed to UV-B and kept in flowing water had increased sustained swimming performance (Ucrit), increased antioxidant defences (catalase activity and glutathione concentrations) and reduced cellular damage (lipid peroxidation and protein carbonyl concentrations) compared with fish in still water. There was no effect of UV-B or water flow on resting or maximal rates of oxygen consumption. Our results show that environmental water flow can alleviate the negative effects of UV-B-induced ROS by increasing defence mechanisms. The resultant reduction in ROS-induced damage may contribute to maintain locomotor performance. Hence, the benefits of regular exercise are ‘transferred’ to improve resilience to the negative impacts of UV-B. Ecologically, the mechanistic link between responses to different habitat characteristics can determine the success of animals. These dynamics have important ecological connotations when river or stream flow changes as a result of weather patterns, climate or human modifications. Highlighted Article: Increased physical activity increases antioxidant defence mechanisms and thereby reduces oxidative stress and increases resilience to the negative effects of UV-B radiation, so that locomotor performance can be maintained in environments exposed to solar radiation.
New hydrazonoindolin-2-ones: Synthesis, exploration of the possible anti-proliferative mechanism of action and encapsulation into PLGA microspheres

The synthesis and molecular characterization of new isatin-based hydrazonoindolin-2-ones 4a-o and 7a-e are reported. The in vitro anti-proliferative potential of the synthesized compounds 4a-o and 7a-e was examined against HT-29 (colon), ZR-75 (breast) and A549 (lung) human cancer cell lines. Compounds 7b, 7d and 7e were the most active congeners against the tested human cancer cell lines with average IC50 values of 4.77, 3.39 and 2.37 μM, respectively, as compared with the reference isatin-based drug, sunitinib, which exhibited an average IC50 value of 8.11 μM. Compound 7e was selected for further pharmacological evaluation in order to gain insight into its possible mechanism of action. It increased caspase 3/7 activity by 2.4- and 1.85-fold between 4 and 8 h of treatment, respectively, at 10 μM and it caused a decrease in the percentage of cells in the G1 phase of the cell cycle with a corresponding increase in the S-phase. In addition, compound 7e increased phosphorylated tyrosine (p-Tyr) levels nearly two-fold with an apparent IC50 value of 3.8 μM. The 7e-loaded PLGA microspheres were prepared using a modified emulsion-solvent diffusion method. The average encapsulation efficiency of the 7e-loaded PLGA microspheres was 85% ± 1.3. While, the in vitro release profile of the 7e-loaded microspheres was characterized by slow and continuous release of compound 7e during 21 days and the release curve was fitted to zero order kinetics. Incorporation of 7e into PLGA microspheres improved its in vitro anti-proliferative activity toward the human cancer cell line A549 after 120 h incubation period with an IC50 value less than 0.8 μM.
Event-related potential correlates of the extraverts' sensitivity to valence changes in positive stimuli

This study investigated whether the human sensitivity to valence intensity changes in positive stimuli varies with extraversion. Event-related potentials were recorded for highly positive, moderately positive, and neutral stimuli while participants (extraverts and nonextraverts) performed a standard/deviant categorization task, irrespective of the emotionality of deviants. The results of extraverts showed larger P2 and P3 amplitudes during highly positive condition than during moderately positive condition which, in turn, elicited larger P2 than neutral condition. Conversely, nonextraverts showed no differences at both P2 and P3 components. Thus, extraverts, unlike less extraverted individuals, are sensitive to valence changes in positive stimuli, which may be underlain by certain biogenetic mechanism.
Swarm‐founding in the polistine wasps: the importance of finding many microsatellite loci in studies of adaptation

We developed 52 microsatellite loci for the wasp, Polybioides tabidus, for the purpose of studying the evolution and inclusive fitness consequences of swarm‐founding. The large number of loci is important for three reasons that may apply to many other systems. Heterozygosity was low in our target species, yet we found enough polymorphic loci for accurate kinship studies in this species. Many monomorphic loci were polymorphic in other polistine wasps, making comparative studies possible. Finally, enough loci amplified over a broad range of species to add a historical dimension. We sequenced six loci in other polistine wasps and used the flanking sequences to construct a phylogeny. Based on this phylogeny, we infer that swarm‐founding has evolved independently three times in the polistine wasps.
A nonlinear speed control for a PM synchronous motor using a simple disturbance estimation technique

A nonlinear speed control for a permanent-magnet (PM) synchronous motor using a simple disturbance estimation technique is presented. By using a feedback linearization scheme, the nonlinear motor model can be linearized in the Brunovski canonical form, and the speed controller can be easily designed based on the linearized model. This technique, however, gives an undesirable output performance under the mismatch of the system parameters and load conditions. An adaptive linearization technique and a sliding-mode control technique have been reported. Although good performance can be obtained, the controller designs are quite complex. To overcome this drawback, the controller parameters are estimated by using a disturbance observer theory where the disturbance torque and flux linkage are estimated. Since only the two reduced-order observers are used for the parameter estimation, the observer designs are considerably simple and the computational load of the controller for parameter estimation is negligibly small. The nonlinear disturbances caused by the incomplete linearization can be effectively compensated by using this control scheme. Thus, a desired dynamic performance and a zero steady-state error can be obtained. The proposed control scheme is implemented on a PM synchronous motor using a digital signal processor (TMS320C31) and the effectiveness is verified through the comparative simulations and experiments.
Myelin acquisition in the central nervous system of the mouse revealed by an MBP-Lac Z transgene

Myelin has pronounced effects upon the morphology, function, and growth of axons in the mammalian CNS. Consequently, oligodendrocyte development and myelination have been investigated using a wide variety of histological, immunocytochemical, ultrastructural, and biochemical techniques. While many of the spatial and temporal features of myelin appearance have been characterized, for any one species only limited regions of the CNS have been investigated. To address this limitation, we have derived transgenic mice in which the bacterial Lac Z gene is regulated by promoter elements of the myelin basic protein gene. When differentiating oligodendrocytes begin to elaborate recognizable myelin, they initiate expression of the MBP-Lac Z transgene and accumulate readily detectable levels of beta-galactosidase. Here, we exploit the sensitivity, resolution, and ease of beta-galactosidase histochemical assays to characterize the temporal and spatial patterns of CNS myelination in the mouse. Many features of the myelination program revealed by this approach were predicted by the immunocytochemical and ultrastructural data derived from other species. Nonetheless, previously undocumented patterns were also encountered. beta-Galactosidase was expressed first by oligodendrocytes in the ventral spinal cord, 1 d prior to birth. There, myelination proceeded in a strictly rostral-caudal direction, whereas in the dorsal cord, myelination initiated in the cervical enlargement and proceeded in both rostral and caudal directions. In the cerebellum, deep regions myelinated first, and in the optic nerve, myelination initiated at the retinal end. In contrast, the lateral olfactory tracts, pons, and optic chiasm initiated myelination along their entire course. (ABSTRACT TRUNCATED AT 250 WORDS)
Mental Health of Iranian High School and College Students

The objectives of this study were to investigate the mental health of Iranian high school and college students with regard to sex differences and to compare the results with those from other countries. The sample included 159 high school students (79 boys, 80 girls) and 160 college students (80 boys, 80 girls). The Middlesex Hospital Questionnaire was used to measure free floating anxiety, depression, phobia, obsession, and somatization. Significant effects of group and sex were noted for phobia, but for depression only the main effect of group was significant. For other scales neither the main effects of group and sex nor their interactions were significant. Iranian college students showed more anxiety than their British peers.
Design Approach for Implementation of Class-J Broadband Power Amplifiers Using Synthesized Band-Pass and Low-Pass Matching Topology

A new synthesis method for the design of broadband impedance matching network has been introduced to match the transistor input. The proposed matching network would be a realistic alternative to those that are frequently designed in low-pass structure. Easy-to-use design equations are given for this filter-based matching network. The required impedance of the stubs and the connecting lines can be directly calculated from the equations. This synthesis method simplifies the implementation of the network in the distributed form as compared with the LC low-pass matching network where equivalences are necessarily required in the rough conversion from lumped-to-distributed elements. The high-efficiency mode of operation is guaranteed by the constructed output low-pass matching network, since the LC low-pass network can provide the prescribed load terminations at fundamental frequencies and at harmonics. A commercially available 10-W GaN HEMT device (CGH40010) was used in this investigation. The proposed broadband power amplifier exhibits band-pass Chebyshev response in S-parameter measurements, and yields good gain flatness (±0.5 dB) and input return loss (>13 dB). Power-added efficiency of 58%–72% has been measured in large-signal measurements. After digital predistortion, the measured adjacent channel leakage power ratio is below −50 dBc at ±5- and ±10-MHz offset, when driven by 5- and 10-MHz WCDMA signals at 7-dB power back off.