Miracle-dz/UniFAR-FTUs huggingface dataset:
Presynaptic Ca2+ Channels and Neurotransmitter Release at the Terminal of a Mouse Cortical Neuron

Regional variation in synaptic efficacy is an important determinant of associative processing as information flows through major circuits of the brain. The perforant path is the principal route of entry from cortex to the hippocampus and contains the first synapse in the cortical–hippocampal projection pathway. We used optical imaging techniques to analyze presynaptic Ca2+ entry and neurotransmitter release at synapses in the medial perforant path linking stellate neurons located in layer II of the entorhinal cortex to granule cells in the dentate gyrus. Similar to other excitatory central synapses, the relationship between neurotransmitter release and the amount of Ca2+ influx can be best described by a Hill equation with a Hill coefficient of 3.5. Our Ca2+ channel toxin studies indicate that P/Q-type channels are the predominant Ca2+ source triggering neurotransmitter release in this pathway, as shown by a potent inhibition of Ca2+ entry and synaptic transmission by the P/Q-type channel blocker ω-agatoxin IVA. However, compared with the downstream hippocampal pyramidal neuron CA3–CA1 synapse, neurotransmitter release was less sensitive to the N-type Ca2+ channel blocker ω-conotoxin GVIA, although the amount of N-type Ca2+ current is comparable. The contribution of N-type channels to neurotransmitter release approximates that found at the CA3–CA1 synapse when tested under lower [Ca2+]o, which effectively reduces the size of the Ca2+ microdomain surrounding each channel. These results suggest that P/Q-type channels are more closely associated with release machinery then N-type channels at this synapse and that cooperativity differences for each channel subtype may characterize variations in signaling at central synapses.
Distribution of oxytocin‐ and vasopressin‐binding sites in the rat extended amygdala: a histoautoradiographic study

Radioligand receptor autoradiography has shown that oxytocin‐ and vasopressin‐binding sites exist in numerous rat brain regions, among which the amygdala and the bed nucleus of the stria terminalis (BST) are especially prominent. However, these descriptions did not take into account the numerous subdivisions of the amygdala and the BST. Thus, we have reinvestigated the distribution of these sites in the rat extended amygdala, which is formed by a continuum of structures stretching from the BST to the centromedial amygdala, including parts of the accumbens nucleus, substantia innominata, and transition areas between the amygdala and the striatum. For this purpose, histoautoradiography was used to detect binding sites at the cellular level, and anatomical boundaries were defined on the basis of acetylcholinesterase histochemistry and tyrosine‐hydroxylase immunohistochemistry. Oxytocin‐ and vasopressin‐binding sites were detected in well‐defined subdivisions of both medial and central parts of the extended amygdala, but they almost never coexisted in the same region. Compared with previously reported distributions, our reinvestigation describes novel oxytocin‐ and vasopressin‐binding sites in the lateral and supracapsular BST, in the sublenticular extended amygdala, in the interstitial nucleus of the posterior limb of the anterior commissure, in the marginal zone, in the central amygdaloid nucleus, and in the anterior amygdaloid area. These results indicate that oxytocin‐ and vasopressin‐binding sites represent an important feature of the extended amygdala and may participate in the large variety of functions that characterize this area, including reproductive and ingestive behaviors, conditioned fear and autonomic regulation. J. Comp. Neurol. 383:305‐325, 1997. © 1997 Wiley‐Liss, Inc.
When is instantaneous frequency the average frequency at each time?

The interpretation of instantaneous frequency has been a subject of interest for many years. One interpretation is that it is the average frequency at each time in the signal. We prove that instantaneous frequency equals the average frequency at each time only when there is symmetry in the instantaneous spectrum, as previous empirical evidence has suggested. Also, when there is such symmetry, the average frequency at each time equals the median frequency at each time.
Nonoperative management of hemodynamically unstable abdominal trauma patients with angioembolization and resuscitative endovascular balloon occlusion of the aorta

BACKGROUND Many hemodynamically stable patients with blunt abdominal solid organ injuries are successfully managed nonoperatively, while unstable patients often require urgent laparotomy. Recently, therapeutic angioembolization has been used in the treatment of intra-abdominal hemorrhage in hemodynamically unstable patients. We undertook this study to review a series of hemodynamically unstable patients with abdominal solid organ injuries managed nonoperatively with angioembolization and resuscitative endovascular balloon occlusion of the aorta. METHODS The institutional review board approved this study. All patients were appropriately resuscitated with transfusions, and angiography was performed after computed tomography. Resuscitative endovascular balloon occlusion of the aorta was performed before computed tomography in all patients. RESULTS Seven patients underwent resuscitative endovascular balloon occlusion of the aorta following severe blunt abdominal trauma. The 28-day survival rate was 86% (6 of 7). There were no complications related to the procedure. CONCLUSION We describe the first clinical series of hemodynamically unstable patients with abdominal solid organ injury treated nonoperatively with angioembolization and resuscitative endovascular balloon occlusion of the aorta. Survival rate was 86%, supporting the need for further study of this modality as an adjunct to the nonoperative management of patients with severe traumatic injuries. LEVEL OF EVIDENCE Therapeutic study, level V.
Systemic Lidocaine Shortens Length of Hospital Stay After Colorectal Surgery: A Double-blinded, Randomized, Placebo-controlled Trial

Objective:To characterize the beneficial effects of perioperative systemic lidocaine on length of hospital stay, gastrointestinal motility, and the inflammatory response after colorectal surgery. Summary Background Data:Surgery-induced stimulation of the inflammatory response plays a major role in the development of several postoperative disorders. Local anesthetics possess anti-inflammatory activity and are thought to positively affect patients' outcome after surgery. This double-blinded, randomized, and placebo-controlled trial aimed to evaluate beneficial effects of systemic lidocaine and to provide insights into underlying mechanisms. Methods:Sixty patients undergoing colorectal surgery, not willing or unable to receive an epidural catheter, were randomly assigned to lidocaine or placebo treatment. Before induction of general anesthesia, an intravenous lidocaine bolus (1.5 mg/kg) was administered followed by a continuous lidocaine infusion (2 mg/min) until 4 hours postoperatively. Length of hospital stay, gastrointestinal motility, and pain scores were recorded and plasma levels or expression of pro- and anti-inflammatory mediators determined. Results:Lidocaine significantly accelerated return of bowel function and shortened length of hospital stay by one day. No difference could be observed in daily pain ratings. Elevated plasma levels of IL-6, IL-8, complement C3a, and IL-1ra as well as expression of CD11b, l- and P-selectin, and platelet-leukocyte aggregates were significantly attenuated by systemic lidocaine. Conclusions:Perioperative intravenous lidocaine not only improved gastrointestinal motility but also shortened length of hospital stay significantly. Anti-inflammatory activity modulating the surgery-induced stress response may be one potential mechanism. Systemic lidocaine may thus provide a convenient and inexpensive approach to improve outcome for patients not suitable for epidural anesthesia.
PET Imaging of Chemokine Receptors in Vascular Injury–Accelerated Atherosclerosis

Atherosclerosis is the pathophysiologic process behind lethal cardiovascular diseases. It is a chronic inflammatory progression. Chemokines can strongly affect the initiation and progression of atherosclerosis by controlling the trafficking of inflammatory cells in vivo through interaction with their receptors. Some chemokine receptors have been reported to play an important role in plaque development and stability. However, the diagnostic potential of chemokine receptors has not yet been explored. The purpose of this study was to develop a positron emitter–radiolabeled probe to image the upregulation of chemokine receptor in a wire-injury-accelerated apolipoprotein E knockout (ApoE−/−) mouse model of atherosclerosis. Methods: A viral macrophage inflammatory protein II (vMIP-II) was used to image the upregulation of multiple chemokine receptors through conjugation with DOTA for 64Cu radiolabeling and PET. Imaging studies were performed at 2 and 4 wk after injury in both wire-injured ApoE−/− and wild-type C57BL/6 mice. Competitive PET blocking studies with nonradiolabeled vMIP-II were performed to confirm the imaging specificity. Specific PET blocking with individual chemokine receptor antagonists was also performed to verify the upregulation of a particular chemokine receptor. In contrast, 18F-FDG PET imaging was performed in both models to evaluate tracer uptake. Immunohistochemistry on the injury and sham tissues was performed to assess the upregulation of chemokine receptors. Results: 15O-CO PET showed decreased blood volume in the femoral artery after the injury. 64Cu-DOTA-vMIP-II exhibited fast in vivo pharmacokinetics with major renal clearance. PET images showed specific accumulation around the injury site, with consistent expression during the study period. Quantitative analysis of tracer uptake at the injury lesion in the ApoE−/− model showed a 3-fold increase over the sham-operated site and the sites in the injured wild-type mouse. 18F-FDG PET showed significantly less tracer accumulation than 64Cu-DOTA-vMIP-II, with no difference observed between injury and sham sites. PET blocking studies identified chemokine receptor–mediated 64Cu-DOTA-vMIP-II uptake and verified the presence of 8 chemokine receptors, and this finding was confirmed by immunohistochemistry. Conclusion: 64Cu-DOTA-vMIP-II was proven a sensitive and useful PET imaging probe for the detection of 8 up-regulated chemokine receptors in a model of injury-accelerated atherosclerosis.
Detection of Respiratory Viral Antigens in Cattle Lung Tissues by Direct ELISA

Bovine Respiratory Disease is one of the most important diseases with serious financial losses for the cattle industry in worldwide. The aim of this study was to detect the associations between respiratory viruses; bovine herpes virus 1, bovine viral diarrhea virus, bovine respiratory syncytial virus, and Para influenza virus 3 statuses of a herd and bovine respiratory disease occurrence. Present study describes virological distribution of bovine respiratory viruses in non-vaccinated cattle (for mentioned infections) of Central Anatolia, Turkey. A total of 24 lung tissue samples were collected during the December 2012 to January 2013 from cattle that died after manifesting clinical signs of respiratory system. Samples were successfully homogenized. Tissue samples were analyzed for detecting antigens by commercially available direct ELISA kit. BRSV antigens were detected in lung tissues 4 out of 24 tested cattle with a percentage of 16.6%, whereas BHV-1, BVDV and PI-3 were not found. BRSV may be common reason of respiratory diseases in herds. It has been also offered advice about prevention of respiratory viral infection for health planning. In conclusion, existence of BRSV infection is still defined and may play an important role in the respiratoric viral infection of cattle.
Genetic and Biochemical Characterization of a 2-Pyrone-4,6-Dicarboxylic Acid Hydrolase Involved in the Protocatechuate 4,5-Cleavage Pathway of Sphingomonas paucimobilis SYK-6

ABSTRACT Sphingomonas paucimobilis SYK-6 is able to grow on a wide variety of dimeric lignin compounds with guaiacyl moieties, which are converted into protocatechuate by the actions of lignin degradation enzymes in this strain. Protocatechuate is a key metabolite in the SYK-6 degradation of lignin compounds with guaiacyl moieties, and it is thought that it degrades to pyruvate and oxaloacetate via the protocatechuate 4,5-cleavage pathway. In a 10.5-kb EcoRI fragment carrying the protocatechuate 4,5-dioxygenase gene (ligAB) (Y. Noda, S. Nishikawa, K. Shiozuka, H. Kadokura, H. Nakajima, K. Yoda, Y. Katayama, N. Morohoshi, T. Haraguchi, and M. Yamasaki. J. Bacteriol. 172:2704–2709, 1990), we found theligI gene encoding 2-pyrone-4,6-dicarboxylic acid (PDC) hydrolase. PDC hydrolase is a member of this pathway and catalyzes the interconversion between PDC and 4-carboxy-2-hydroxymuconic acid (CHM). The ligI gene is thought to be transcribed divergently fromligAB and consists of an 879-bp open reading frame encoding a polypeptide with a molecular mass of 32,737 Da. The ligIgene product (LigI), expressed in Escherichia coli, was purified to near-homogeneity and was estimated to be a monomer (31.6 kDa) by gel filtration chromatography. The isoelectric point was determined to be 4.9. The optimum pH for hydrolysis of PDC is 8.5, the optimum pH for synthesis of PDC is 6.0 to 7.5, and theKm values for PDC and CHM are 74 and 49 μM, respectively. LigI activity was inhibited by the addition of thiol reagents, suggesting that the cysteine residue is a catalytic site. LigI is more resistant to metal ion inhibition than the PDC hydrolases of Pseudomonas ochraceae (K. Maruyama, J. Biochem. 93:557–565, 1983) and Comamonas testosteroni (P. J. Kersten, S. Dagley, J. W. Whittaker, D. M. Arciero, and J. D. Lipscomb, J. Bacteriol. 152:1154–1162, 1982). The insertional inactivation of the ligI gene in S. paucimobilis SYK-6 led to the complete loss of PDC hydrolase activity and to a growth defect on vanillic acid; it did not affect growth on syringic acid. These results indicate that theligI gene is essential for the growth of SYK-6 on vanillic acid but is not responsible for the growth of SYK-6 on syringic acid.
Neural Coding Mechanisms Underlying Perceived Roughness of Finely Textured Surfaces

Combined psychophysical and neurophysiological studies have shown that the perceived roughness of surfaces with element spacings of >1 mm is based on spatial variation in the firing rates of slowly adapting type 1 (SA1) afferents (mean absolute difference in firing rates between SA1 afferents with receptive fields separated by ∼2 mm). The question addressed here is whether this mechanism accounts for the perceived roughness of surfaces with element spacings of <1 mm. Twenty triangular and trapezoidal gratings plus a smooth surface were used as stimulus patterns [spatial periods, 0.1–2.0 mm; groove widths (GWs), 0.1–2.0 mm; and ridge widths (RWs), 0–1.0 mm]. In the human psychophysical studies, we found that the following equation described the mean roughness magnitude estimates of the subjects accurately (0.99 correlation): 0.2 + 1.6GW − 0.5RW − 0.25GW2. In the neurophysiological studies, these surfaces were scanned across the receptive fields of SA1, rapidly adapting, and Pacinian (PC) afferents, innervating the glabrous skin of anesthetized macaque monkeys. SA1 spatial variation was highly correlated (0.97) with human roughness judgments. There was no consistent relationship between PC responses and roughness judgments; PC afferents responded strongly and almost equally to all of the patterns. Spatial variation in SA1 firing rates is the only neural code that accounts for the perceived roughness of surfaces with finely and coarsely spaced elements. When surface elements are widely spaced, the spatial variation in firing rates is determined primarily by the surface pattern; when the elements are finely spaced, the variation in firing rates between SA1 afferents is determined by stochastic variation in spike rates.
Prostaglandin F 2 stimulates growth of skeletal muscle cells via an NFATC 2-dependent pathway

keletal muscle growth requires multiple steps to form large multinucleated muscle cells. Molecules that stimulate muscle growth may be therapeutic for muscle loss associated with aging, injury, or disease. However, few factors are known to increase muscle cell size. We demonstrate that prostaglandin F 2 (PGF 2 ) as well as two analogues augment muscle cell size in vitro. This increased myotube size is not due to PGF 2 -enhancing cell fusion that initially forms myotubes, but rather to PGF 2 recruiting the fusion of cells with preexisting multinucleated cells. This growth is mediated through the PGF 2 receptor (FP receptor). As the FP receptor can increase levels of intracellular calcium, the S involvement of the calcium-regulated transcription factor nuclear factor of activated T cells (NFAT) in mediating PGF 2 -enhanced cell growth was examined. We show that NFAT is activated by PGF 2 , and the isoform NFATC2 is required for PGF 2 -induced muscle cell growth and nuclear accretion, demonstrating the first intersection between prostaglandin receptor activation and NFAT signaling. Given this novel role for PGF 2 in skeletal muscle cell growth, these studies raise caution that extended use of drugs that inhibit PG production, such as nonsteroidal antiinflammatory drugs, may be deleterious for muscle growth.
Is Rationality Normative

Rationality requires various things of you. For example, it requires you not to have contradictory beliefs, and to intend what you believe is a necessary means to an end that you intend. Suppose rationality requires you to F. Does this fact constitute a reason for you to F? Does it even follow from this fact that you have a reason to F? I examine these questions and reach a sceptical conclusion about them. I can find no satisfactory argument to show that either has the answer 'yes'. I consider the idea that rationality is normative for instrumental reasons, because it helps you to achieve some of the things you ought to achieve. I also consider the idea that rationality consists in responding correctly to reasons. I reject both. 1. The normative question Rationality requires various things of you. For example, it requires you not to have contradictory beliefs, to believe what follows by modus ponens from things you believe, to intend what you believe to be a necessary means to an end that you intend, and to intend to do what you believe you ought to do. These are only rough formulations, and rough formulations are perhaps enough for this paper. However, for the sake of accuracy, I shall give more formal statements of the requirement that you believe what follows by modus ponens from things you believe, and the requirement that you intend to do what you believe you ought to do. These ones will come up later in the paper. They are: Modus ponens. Rationality requires of N that, if N believes p and N believes that if p then q, and if it matters to N whether q, then N believes q. Krasia. Rationality requires of N that, if N believes that she herself ought to F, and if N believes that she herself will F if and only if she herself intends to F, then N intends to F.
Spatiotemporal Conversion of Auditory Information for Cochleotopic Mapping

Auditory communication signals such as monkey calls are complex FM vocal sounds and in general induce action potentials in different timing in the primary auditory cortex. Delay line scheme is one of the effective ways for detecting such neuronal timing. However, the scheme is not straightforwardly applicable if the time intervals of signals are beyond the latency time of delay lines. In fact, monkey calls are often expressed in longer time intervals (hundreds of milliseconds to seconds) and are beyond the latency times observed in the brain (less than several hundreds of milliseconds). Here, we propose a cochleotopic map similar to that in vision known as a retinotopic map. We show that information about monkey calls could be mapped on a cochleotopic cortical network as spatiotemporal firing patterns of neurons, which can then be decomposed into simple (linearly sweeping) FM components and integrated into unified percepts by higher cortical networks. We suggest that the spatiotemporal conversion of auditory information may be essential for developing the cochleotopic map, which could serve as the foundation for later processing, or monkey call identification by higher cortical areas.
On building software process models under the lamppost

Most software process models are based on the management tracking and control of a project. The popular alternatives to these models such as rapid prototyping and program transformation are built around specific technologies, many of which are still in their adolescence. Neither of these approaches describe the actual processes that occur during the development of a software system. That is, these models focus on the series of artifacts that exist at the end of phases of the process, rather than on the actual processes that are conducted to create the artifacts. We conducted a field study of large system development projects to gather empirical information about the communication and technical decision-making processes that underlie the design of such systems. The findings of this study are reviewed for their implications on modeling the process of designing large software systems. The thesis of the paper is that while there are many foci for process models, the most valuable are those which capture the processes that control the most variance in software productivity and quality.
TopA, the Sulfolobus solfataricus topoisomerase III, is a decatenase

Abstract DNA topoisomerases are essential enzymes involved in all the DNA processes and among them, type IA topoisomerases emerged as a key actor in the maintenance of genome stability. The hyperthermophilic archaeon, Sulfolobus solfataricus, contains three topoisomerases IA including one classical named TopA. SsoTopA is very efficient at unlinking DNA catenanes, grouping SsoTopA into the topoisomerase III family. SsoTopA is active over a wide range of temperatures and at temperatures of up to 85°C it produces highly unwound DNA. At higher temperatures, SsoTopA unlinks the two DNA strands. Thus depending on the temperature, SsoTopA is able to either prevent or favor DNA melting. While canonical topoisomerases III require a single-stranded DNA region or a nick in one of the circles to decatenate them, we show for the first time that a type I topoisomerase, SsoTopA, is able to efficiently unlink covalently closed catenanes, with no additional partners. By using single molecule experiments we demonstrate that SsoTopA requires the presence of a short single-stranded DNA region to be efficient. The unexpected decatenation property of SsoTopA probably comes from its high ability to capture this unwound region. This points out a possible role of TopA in S. solfataricus as a decatenase in Sulfolobus.