Miracle-dz/UniFAR-FTUs huggingface dataset:
Characterization of the regulation and function of zinc‐dependent histone deacetylases during rodent liver regeneration

The studies reported here were undertaken to define the regulation and functional importance of zinc‐dependent histone deacetylase (Zn‐HDAC) activity during liver regeneration using the mouse partial hepatectomy (PH) model. The results showed that hepatic HDAC activity was significantly increased in nuclear and cytoplasmic fractions following PH. Further analyses showed isoform‐specific effects of PH on HDAC messenger RNA (mRNA) and protein expression, with increased expression of the class I HDACs, 1 and 8, and class II HDAC4 in regenerating liver. Hepatic expression of (class II) HDAC5 was unchanged after PH; however, HDAC5 exhibited transient nuclear accumulation in regenerating liver. These changes in hepatic HDAC expression, subcellular localization, and activity coincided with diminished histone acetylation in regenerating liver. The significance of these events was investigated by determining the effects of suberoylanilide hydroxyamic acid (SAHA, a specific inhibitor of Zn‐HDAC activity) on hepatic regeneration. The results showed that SAHA treatment suppressed the effects of PH on histone deacetylation and hepatocellular bromodeoxyuridine (BrdU) incorporation. Further examination showed that SAHA blunted hepatic expression and activation of cell cycle signals downstream of induction of cyclin D1 expression in mice subjected to PH. Conclusion: The data reported here demonstrate isoform‐specific regulation of Zn‐HDAC expression, subcellular localization, and activity in regenerating liver. These studies also indicate that HDAC activity promotes liver regeneration by regulating hepatocellular cell cycle progression at a step downstream of cyclin D1 induction. (HEPATOLOGY 2013)
Validity of diagnoses in the general practice research database.

The article by Khan and colleagues1 highlights the strength of the General Practice Research Database (GPRD) as a research-quality database providing accurate diagnostic data to researchers on a wide range of conditions, and for millions of patients. While the search strategy for this study was broad and inclusive of prescription data, procedures, and smoking in addition to diagnoses, the authors did not identify as many articles as expected. We published a similar systematic review of the validity of diagnoses in the GPRD2 and found …
Human spongiform encephalopathy: The national institutes of health series of 300 cases of experimentally transmitted disease

We present a synthesis of clinical, neuropathological, and biological details of the National Institutes of Health series of 300 experimentally transmitted cases of spongiform encephalopathy from among more than 1,000 cases of various neurological disorders inoculated into nonhuman primates during the past 30 years. The series comprises 278 subjects with Creutzfeldt‐Jakob disease, of whom 234 had sporadic, 36 familial, and 8 iatrogenic disease; 18 patients with kuru; and 4 patients with Gerstmann‐Sträussler‐Scheinker syndrome. Sporadic Creutzfeldt‐Jakob disease, numerically by far the most important representative, showed an average age at onset of 60 years, with the freqauent early appearance of cerebellar and visual/oculomotor signs, and a broad spectrum of clinical features during the subsequent course of illness, which was usually fatal in less than 6 months. Characteristic spongiform neuropathology was present in all but 2 subjects. Microscopically visible kuru‐type amyloid plaques were found in 5% of patients with Creutzfeldt‐Jakob disease, 75% of those with kuru, and 100% of those with Gerstmann‐Sträussler‐Scheinker syndrome; brain biopsy was diagnostic in 95% of cases later confirmed at autopsy, and proteinase‐resistant amyloid protein was identified in Western blots of brain extracts from 88% of tested subjects. Experimental transmission rates were highest for iatrogenic Creutzfeldt‐Jakob disease (100%), kuru (95%), and sporadic Creutzfeldt‐Jakob disease (90%), and considerably lower for most familial forms of disease (68%). Incubation periods as well as the durations and character of illness showed great variability, even in animals receiving the same inoculum, mirroring the spectrum of clinical profiles seen in human disease. Infectivity reached average levels of nearly 105 median lethal doses/gm of brain tissue, but was only irregularly present (and at much lower levels) in tissues outside the brain, and except for cerebrospinal fluid, was never detected in bodily secretions or excretions.
Differential diagnosis of atypical focal peripheral neuropathy: Case report

Carpal tunnel syndrome (CTS) is the most frequent form of focal peripheral neuropathy but is commonly misdiagnosed. The aim of this case report was to describe the differential diagnosis of CTS and atypical focal peripheral neuropathy in a 34-year-old female. Although the patient's medical diagnosis was CTS, she did not report night pain, did not exhibit hand atrophy, had no sensory loss, did not meet the five criteria of the clinical prediction rule for CTS, and demonstrated symptoms associated with radial and median nerve pain. The patient's concordant symptoms were associated with wrist passive accessory stiffness and functional activities that required repetitive end range movements. Interventions included treatment of two priority impairments: 1) pain and 2) wrist accessory stiffness. After five treatments, the patient no longer reported pain with activities and was able to return to work with no restrictions. Although the patient in this case report exhibited isolated features consistent with CTS, compelling cumulative evidence suggested a distinct diagnosis. Limited evidence exists to support the use of mobilization, strengthening, and pain reduction-based modalities for the treatment of focal peripheral neuropathy; subsequently, treatments must be individually effective when targeted toward the patient's priority impairments. The diagnosis of CTS is challenging because there are a variety of possible clinical presentations. Using evidence-based indices, such as the clinical prediction rule for CTS and other comparative history and physical measures, should improve the likelihood of accurate diagnosis and treatment.
Variations in the Pacific Decadal Oscillation over the past millennium

Hydrologically sensitive tree‐ring chronologies from Pinus flexilis in California and Alberta were used to produce an AD 993–1996 reconstruction of the Pacific Decadal Oscillation (PDO) and to assess long‐term variability in the PDO's strength and periodicity. The reconstruction indicates that a ∼50 to 70 year periodicity in the PDO is typical for the past 200 years but, was only intermittently a strong mode of variability prior to that. Between AD 1600 and 1800 there is a general absence of significant variability within the 50 to 100 year frequency range. Significant variability within in the frequency range of 50 to 100 years reemerges between AD 1500 and 1300 and AD 1200 to 1000. A prolonged period of strongly negative PDO values between AD 993 and 1300 is contemporaneous with a severe medieval megadrought that is apparent in many proxy hydrologic records for the western United States and Canada.
Optimal Ecodriving Control: Energy-Efficient Driving of Road Vehicles as an Optimal Control Problem

Transportation is responsible for a substantial fraction of worldwide energy consumption and greenhouse gas emissions and is the largest sector after energy production. However, while emissions from other sectors are generally decreasing, those from transportation have increased since 1990. Reducing the impact of transportation is a task that is inherently associated with the improvement of energy efficiency, particularly for passenger cars that contribute to almost half of the whole sector.
The anti-metastatic efficacy of β-ionone and the possible mechanisms of action in human hepatocarcinoma SK-Hep-1 cells

β-Ionone (BI), a precursor for carotenoids, is widely distributed in fruit and vegetables. Recent in vitro studies have demonstrated the potential anti-metastatic effects of BI, but the mechanisms underlying such actions are not clear. Because liver cancer is the most endemic cancer in Taiwan and in a large region of the world, we hereby investigate the anti-metastatic effects of BI and its mechanisms of actions in a highly metastatic human hepatocarcinoma SK-Hep-1 cells. We show that incubation of cells with BI (1–50 μm) for 24 and 48 h significantly inhibited cell invasion, migration and adhesion. Mechanistically, incubation of cells with BI (1–50 μm) for 24 h resulted in the following: (1) significant inhibition of matrix metalloproteinase (MMP)-2, MMP-9 and urokinase-type plasminogen activator activities, (2) up-regulation of protein expression of the tissue inhibitor of matrix metalloproteinase (TIMP)-1, TIMP-2 and plasminogen activator inhibitor-1, (3) down-regulation of the expression of migration-related proteins, including focal adhesion kinase (FAK), phosphorylated form of FAK, Rho, Rac1 and Cdc42 and (4) up-regulation of the expression of nm23-H1 protein (P < 0·05). Overall, the results show that BI effectively inhibits the metastasis of SK-Hep-1 cells, and this effect involves the regulation of gene expression and signal pathways related to invasion and migration.
Analysis of organ motion effects on the effective fluences for liver IMRT

An effective fluence concept was employed to make forward dose calculations to investigate the effects of a distorted fluence map on dose plans. Fluence changes caused by organ motion were calculated using Chui's algorithm (2003 Med. Phys. 30 1736). In two test cases with various fluence maps, the effects of motion were simulated using a maximal displacement from 5 mm to 25 mm; 108 fluence maps that were calculated from 16 IMRT plans for eight liver cancer patients were analyzed and compared with and without gating. Fluoroscopic measurements were made of a moving diaphragm in this study. Fluence changes associated with superior–inferior organ motion, perpendicular to the moving MLC, were also examined. The effects of motion on the fluence maps were evaluated from both the fluence differences between static and motion and the χ function. The maximum displacements of the organs in all of these cases were analyzed and correlated with the change in fluence generated from the liver IMRT plans. The dosimetric effects on the target coverage were evaluated for each plan. The results indicate that, for the same fluence map, the mean fluence intensity error or the percentage of the fluence points that have an unacceptable error is linearly related to the extent of motion. For different fluence maps, the degree to which the fluence is distorted by motion is strongly related to the product of the motion extent and the fluence gradient in the direction of diaphragm motion. For eight liver patients and 16 IMRT plans in this work (with gated technique, motion extent from 0.5 cm to 1.0 cm; without gated technique, motion extent from 0.9 cm to 1.8 cm), the fluence modulations are mild, such that the respiratory motion of each patient did not strongly affect the CTV coverage. The mean dose error is 1.5% for free motion (0.9–1.8 cm) and is around 1% for gated motion (0.5–1 cm).
Cytokine upregulation of surface antigens correlates to the priming of the neutrophil oxidative burst response

Neutrophil activation is strongly related to organ dysfunction that occurs during systemic inflammatory responses. The aim of our study was to analyze the oxidative burst response in correlation to the up‐ and downregulation of N‐formyl‐L‐methionyl‐L‐leucyl‐phenylalanine (fMLP) receptors and the surface antigens CD11b, CD62L, and CD66b as potential surrogate markers of the degree of neutrophil priming for an increased oxidative burst response induced by proinflammatory cytokines.
Neisseria meningitidis: epidemiology, treatment and prevention in adolescents

Purpose of review Neisseria meningitidis has been recognized as a cause of serious disease for centuries, but changing epidemiology and advances in treatment and prevention strategies mandate that providers be aware of ongoing developments with regard to this infection. Given the high burden of disease in adolescents, it is important for clinicians to be familiar with current recommendations regarding N. meningitidis. Recent findings Adolescents and young adults continue to have the second highest incidence of disease from N. meningitidis. New diagnostic techniques, including polymerase chain reaction, have shown promise for enhancing detection of meningococcal infection in selected scenarios. Whereas most isolates of meningococcus remain penicillin-susceptible, fluoroquinolone resistance has now been documented in the US for the first time. Routine immunization using the meningococcal conjugate vaccine continues to be recommended, despite ongoing concern about a possible association between vaccination and Guillain–Barré syndrome. Active research is ongoing to develop a serogroup B vaccine and meningococcal vaccines that are immunogenic in infants and toddlers. Summary Given the increased incidence of meningococcal infection among adolescents and the substantial morbidity and mortality associated with invasive disease, adolescent health providers must be familiar with current antibiotic treatment and prophylaxis guidelines and ongoing developments regarding meningococcal vaccination.
Estimating the Cost of Variable Annuity Guaranteed Minimum Withdrawal Benefit

In this work, we present a very simple model of providing an upper bound for the costs of the guaranteed minimum withdrawal benefit in variable annuities. The upper bound is in closed form based on the Black-Scholes formulas. The value of this simple model is its simplicity, and its conformation with some of the known results of the more complex models.
Comparative study of condylar settings of three semiadjustable articulators.

The reproducibility of arcon semiadjustable Whip Mix, Denar Mark II, and Hanau 158 articulators was tested using multiple protrusive and lateral edge-to-edge wax interarch registrations made with an interocclusal device. Photographic and cephalometric tracings verified an identical angulation between the axis-orbital craniofacial reference plane and the maxillary occlusal plane for the subject and both the Denar Mark II and Hanau 158 articulators. This angle was 2.5 degrees less in the Whip Mix instrument. Three operators made three settings for each of 12 protrusive and 24 lateral interarch registrations for each articulator. Results showed significant differences between instruments. Whip Mix consistently gave the highest.angulations and Hanau 158 the lowest. For protrusive records there was no significant difference between examiners, but for lateral records a significant difference in examiner registration was found. For both protrusive and nonworking registrations, interaction was seen between instrument and operator and between instrument and registration, and a significant difference was seen between records. This study supports previous studies showing that semiadjustable articulators using interarch records have a low level of reproducibility and are subject to variables of instrument, operator, and occlusal records.
Avascular Necrosis of the Talus After McKay Clubfoot Release for Idiopathic Congenital Clubfoot

Avascular necrosis of the talus is a serious potential complication of clubfoot surgery. In the few cases described in the literature, the necrosis has involved the entire talus and resulted in progressive fragmentation and collapse. Serial postoperative radiographs of 96 idiopathic clubfeet in 70 patients are reviewed here to determine the incidence of avascular necrosis after McKay soft tissue release. Based on criteria in the literature for making the diagnosis, no cases of avascular necrosis were seen. Growth lines were observed in the cuboids and calcanei of all the feet during the follow-up period. Eight feet failed to develop growth lines in the talus during follow-up. Five of these feet showed flattening of the dome of the talus and three hypoplasia of the talar head and neck at the most recent follow-up. Absence of normal growth lines in the talus after operation seems to predict talar abnormalities.
A Rare Combination of Ribonucleotide Reductases in the Social Amoeba Dictyostelium discoideum*

Background: Dictyostelium discoideum encodes both class I and II RNRs. Results: Both RNRs are expressed in D. discoideum, and depletion of class I RNR drastically reduces spore formation and viability. Conclusion: Class I RNR is central for D. discoideum growth and differentiation, whereas class II function is enigmatic. Significance: Our results underscore the evolutionary selection for this rare set of RNRs in D. discoideum. Ribonucleotide reductases (RNRs) catalyze the only pathway for de novo synthesis of deoxyribonucleotides needed for DNA replication and repair. The vast majority of eukaryotes encodes only a class I RNR, but interestingly some eukaryotes, including the social amoeba Dictyostelium discoideum, encode both a class I and a class II RNR. The amino acid sequence of the D. discoideum class I RNR is similar to other eukaryotic RNRs, whereas that of its class II RNR is most similar to the monomeric class II RNRs found in Lactobacillus spp. and a few other bacteria. Here we report the first study of RNRs in a eukaryotic organism that encodes class I and class II RNRs. Both classes of RNR genes were expressed in D. discoideum cells, although the class I transcripts were more abundant and strongly enriched during mid-development compared with the class II transcript. The quaternary structure, allosteric regulation, and properties of the diiron-oxo/radical cofactor of D. discoideum class I RNR are similar to those of the mammalian RNRs. Inhibition of D. discoideum class I RNR by hydroxyurea resulted in a 90% reduction in spore formation and decreased the germination viability of the surviving spores by 75%. Class II RNR could not compensate for class I inhibition during development, and an excess of vitamin B12 coenzyme, which is essential for class II activity, did not improve spore formation. We suggest that class I is the principal RNR during D. discoideum development and growth and is important for spore formation, possibly by providing dNTPs for mitochondrial replication.
2′-Ethoxy-5′-Methoxy-2-(5-Methylthienyl)Chalcone Inhibits Collagen-Induced Protein Tyrosine Phosphorylation and Thromboxane Formation during Platelet Aggregation and Adhesion

Subendothelial collagen supports platelet adhesion, activation, and thrombus growth at sites of vascular damage. Previous studies have shown that chalcones possess antiplatelet activity, but their mechanism of action is not fully understood. In this study, a recently synthesized chalcone, 2′-ethoxy-5′-methoxy-2-(5-methylthienyl)chalcone (EMMTC), was used to investigate chalcone effects on platelet aggregation and adhesion. We found that EMMTC potently inhibited collagen-induced platelet aggregation with an IC50 of 1.01 μmol/l. In contrast, it did not inhibit thrombin- and ADP-induced platelet aggregation. EMMTC could inhibit arachidonic acid (AA)-induced platelet aggregation and collagen- and AA-induced thromboxane B2 (TXB2) formation, suggesting that cyclooxygenase and/or thromboxane synthase were affected during this process. Moreover, EMMTC suppressed collagen-induced protein tyrosine phosphorylation, including phospholipase C-γ2 (PLC-γ2), phosphatidylinositol-3 kinase (PI-3K), Src, Fyn and LAT. Strikingly, EMMTC also blocked platelet adhesion to immobilized collagen and convulxin (a snake venom-derived protein that activates platelet glycoprotein VI receptor). The attenuation of phosphorylation of focal adhesion kinase (FAK) was observed during adhesion. Taken together, our results presented here demonstrate that the chalcone derivative EMMTC affects collagen-induced protein tyrosine phosphorylation and TXB2 formation and functionally blocks collagen-induced platelet aggregation and adhesion.
Improving electrokinetic microdevice stability by controlling electrolysis bubbles

The voltage‐operating window for many electrokinetic microdevices is limited by electrolysis gas bubbles that destabilize microfluidic system causing noise and irreproducible responses above ∼3 V DC and less than ∼1 kHz AC at 3 Vpp. Surfactant additives, SDS and Triton X‐100, and an integrated semipermeable SnakeSkin® membrane were employed to control and assess electrolysis bubbles from platinum electrodes in a 180 by 70 μm, 10 mm long microchannel. Stabilized current responses at 100 V DC were observed with surfactant additives or SnakeSkin® barriers. Electrolysis bubble behaviors, visualized via video microscopy at the electrode surface and in the microchannels, were found to be influenced by surfactant function and SnakeSkin® barriers. Both SDS and Triton X‐100 surfactants promoted smaller bubble diameters and faster bubble detachment from electrode surfaces via increasing gas solubility. In contrast, SnakeSkin® membranes enhanced natural convection and blocked bubbles from entering the microchannels and thus reduced current disturbances in the electric field. This data illustrated that electrode surface behaviors had substantially greater impacts on current stability than microbubbles within microchannels. Thus, physically blocking bubbles from microchannels is less effective than electrode functionalization approaches to stabilize electrokinetic microfluidic systems.
Loss of motor function in preclinical Alzheimer’s disease

Accumulating evidence suggests that Alzheimer’s disease (AD) has a long preclinical phase, during which time its characteristic pathology accumulates and patient function declines, but symptoms are insufficient to warrant a clinical diagnosis of dementia. There have been increasing reports of noncognitive symptoms, including loss of motor function, reported to be associated with incident AD. To understand the link between motor function and preclinical AD, this article examines: our understanding of motor function and its clinical assessment in cohort studies; the relationship of motor function and loss of cognition in older persons; risk factors for cognitive and motor decline; and the relation of post-mortem indices of AD and motor function prior to death. Together, these data suggest that age-related cognitive and motor decline may share a common causation. Furthermore, individuals with a clinical diagnosis of AD may represent the ‘tip of the iceberg’, since AD pathology may also account for a substantial proportion of cognitive and motor dysfunction currently considered ‘normal aging’ in older persons without dementia. Thus, AD may have a much larger impact on the health and wellbeing of our aging population
Active stabilization control strategy for storage system paralleled with constant power loads

In DC Microgrid, the majority of the loads are connected to the grid via power electronic converters. These loads act as constant power loads (CPLs) when tightly regulated. If the voltage changes, the CPLs behave negative incremental impedance characteristic during dynamic periods, and could cause system instability. To guarantee the system stability and simultaneously maintain the CPLs good performances, this paper utilizes an active stabilization control strategy for the battery converter paralleled with CPLs. Based on the mixed potential theory, the large signal models of the storage system and the CPLs are established. The control strategy considers the negative incremental impedance of the CPLs in the outer control loop, and consequently, the converter with the proposed strategy could actively and quickly compensate the CPLs during large disturbances. The stability constraint is very simple and easy to be implemented. The simulation results validate the effectiveness of the active stabilization control strategy.