Miracle-dz/UniFAR-FTUs huggingface dataset:
Interruption of β-Catenin Signaling Reduces Neurogenesis in Alzheimer's Disease

The neuronal loss associated with Alzheimer's disease (AD) affects areas of the brain that are vital to cognition. Although recent studies have shown that new neurons can be generated from progenitor cells in the neocortices of healthy adults, the neurogenic potential of the stem/progenitor cells of AD patients is not known. To answer this question, we compared the properties of glial progenitor cells (GPCs) from the cortices of healthy control (HC) and AD subjects. The GPCs from AD brain samples displayed reduced renewal capability and reduced neurogenesis compared with GPCs from HC brains. To investigate the mechanisms underlying this difference, we compared β-catenin signaling proteins in GPCs from AD versus HC subjects and studied the effect of amyloid β peptide (Aβ, a hallmark of AD pathology) on GPCs. Interestingly, GPCs from AD patients exhibited elevated levels of glycogen synthase kinase 3β (GSK-3β, an enzyme known to phosphorylate β-catenin), accompanied by an increase in phosphorylated β-catenin and a decrease in nonphosphorylated β-catenin compared with HC counterparts. Furthermore. we found that Aβ treatment impaired the ability of GPCs from HC subjects to generate new neurons and caused changes in β-catenin signaling proteins similar to those observed in GPCs from AD patients. Similar results were observed in GPCs isolated from AD transgenic mice. These results suggest that Aβ-induced interruption of β-catenin signaling may contribute to the impairment of neurogenesis in AD progenitor cells.
Influence of oral beta-alanine and L-histidine supplementation on the carnosine content of the gluteus medius.

The aim of this work was to test the hypothesis that in vivo carnosine biosynthesis is dependent upon endogenous beta-alanine availability, by studying the effect of sustained dietary beta-alanine supplementation in the horse on the carnosine concentration in types I, IIA and IIB skeletal muscle fibres. The diets of 6 Thoroughbred horses were supplemented 3 times/day with beta-alanine (100 mg/kg bwt) and L-histidine (12.5 mg/kg bwt) for a period of 30 days. Percutaneous biopsies of the m. gluteus medius from a depth of 6 cm were taken on the days immediately before and after the supplementation period. Heparinised blood samples were collected at hourly intervals on the first and last days of supplementation, and on every sixth day during the supplementation period, 2 h after each ration. Individual muscle fibres were dissected from freeze-dried biopsies, weighed and characterised histochemically. beta-alanine, histidine and carnosine concentrations were measured in plasma. The areas under the plasma concentration-time curves (AUC) for beta-alanine and histidine were calculated as indicators of the doses absorbed. Carnosine concentrations were measured in types I, IIA and IIB muscle fibres. There was an adaptive response to sustained beta-alanine administration resulting in mean +/- s.d. beta-alanine AUC increasing significantly from 1130 +/- 612 mumol/l h (Day 1) to 2490 +/- 1416 mumol/l h (Day 30) (P < 0.05). This was probably due to increased beta-amino acid transport across the gastrointestinal lumen. There was no consistent increase in histidine AUC between Days 1 and 30, (mean +/- s.d. values being 757 +/- 447 mumol/l h Day 1[ and 1162 +/- 1084 mumol/l h Day 30[ P > 0.05[). Type IIA fibre carnosine concentrations increased from 59.9-102.6 to 76.2-112.2 mmol/kg dry weight (dw). Increases were statistically significant in 2 of the 6 horses (P < 0.05 in both instances). Type IIB fibre carnosine concentrations increased from 101.3-131.2 to 114.3-153.3 mmol/kg dw. Increases were statistically significant in 5 of the 6 horses (P < 0.05 in 3 horses, P < 0.01 in 1 horse, P < 0.005 in 1 horse). Changes in muscle carnosine concentration appeared to be influenced by beta-alanine bioavailability. Individual increases in muscle carnosine concentration were significantly correlated with individual changes in beta-alanine AUC (r2 = 0.973, P < 0.005). Increased muscle carnosine concentrations lead to increased intramuscular hydrogen ion (H+) buffering capacity.
In Situ Bypass in the Management of Complex Intracranial Aneurysms: Technique Application in 13 Patients

OBJECTIVE: Cerebral revascularization is an important part of the treatment of complex intracranial aneurysms that require deliberate occlusion of a parent artery. In situ bypass brings together intracranial donor and recipient arteries that lie parallel and in close proximity to one another rather than using an extracranial donor artery. An experience with in situ bypasses was retrospectively reviewed. METHODS: Thirteen aneurysms were treated with in situ bypasses between 1997 and 2004. During this time, 1071 aneurysms were treated microsurgically and 46 bypasses were performed as part of the aneurysm treatment. RESULTS: Treated aneurysms were located at the middle cerebral artery (MCA) in five patients, posteroinferior cerebellar artery (PICA) in three patients, vertebral artery in three patients, and anterior communicating artery in two patients. Seven aneurysms were fusiform or dolichoectatic, and six aneurysms were saccular. Microsurgical revascularization techniques included side-to-side anastomosis of intracranial arteries in eight patients and aneurysm excision with end-to-end reanastomosis of the parent artery in five patients. In situ bypasses included A3–A3 anterior cerebral artery bypass in two patients, anterior temporal artery-MCA bypass in one patient, MCA–MCA bypass in one patient, and PICA–PICA bypass in four patients. Aneurysm excision with arterial reanastomosis included three MCA aneurysms and two PICA aneurysms. On angiography, all aneurysms were completely obliterated and 12 bypasses were patent. CONCLUSION: In situ bypass is a safe and effective alternative to extracranial-intracranial bypasses and high-flow bypasses using saphenous vein or radial artery grafts. Although in situ bypasses are more demanding technically, they do not require harvesting a donor artery, can be accomplished with one anastomosis, and are less vulnerable to injury or occlusion.
Pre-impact lower extremity posture and brake pedal force predict foot and ankle forces during an automobile collision.

BACKGROUND The purpose of this study was to determine how a driver's foot and ankle forces during a frontal vehicle collision depend on initial lower extremity posture and brake pedal force. METHOD OF APPROACH A 2D musculoskeletal model with seven segments and six right-side muscle groups was used. A simulation of a three-second braking task found 3647 sets of muscle activation levels that resulted in stable braking postures with realistic pedal force. These activation patterns were then used in impact simulations where vehicle deceleration was applied and driver movements and foot and ankle forces were simulated. Peak rearfoot ground reaction force (F(RF)), peak Achilles tendon force (FAT), peak calcaneal force (F(CF)) and peak ankle joint force (F(AJ)) were calculated. RESULTS Peak forces during the impact simulation were 476 +/- 687 N (F(RF)), 2934 +/- 944 N (F(CF)) and 2449 +/- 918 N (F(AJ)). Many simulations resulted in force levels that could cause fractures. Multivariate quadratic regression determined that the pre-impact brake pedal force (PF), knee angle (KA) and heel distance (HD) explained 72% of the variance in peak FRF, 62% in peak F(CF) and 73% in peak F(AJ). CONCLUSIONS Foot and ankle forces during a collision depend on initial posture and pedal force. Braking postures with increased knee flexion, while keeping the seat position fixed, are associated with higher foot and ankle forces during a collision.
LncRNA ATB promotes proliferation and metastasis in A549 cells by down‐regulation of microRNA‐494

Lung cancer is a commonly diagnosed disease with poor prognosis. Novel therapeutic targets and deep understanding of the regulatory mechanisms in lung cancer are of great importance. We aimed to figure out the functional roles of lncRNA‐activated by transforming growth factor‐β (ATB) in A549 cells as well as the underlying molecular mechanisms. ATB was non‐physiologically expressed in A549 cells after cell transfection. Then, cell proliferation, expressions of proteins related to proliferation and epithelial‐mesenchymal transition (EMT), migration, and invasion were measured by BrdU incorporation assay, Western blot analysis, and Transwell assay, respectively. Afterwards, miR‐494 expression in transfected A549 cells was determined by quantitative reverse transcription PCR. Meanwhile, effects of miR‐494 overexpression on ATB‐overexpressed cells were assessed. Finally, the phosphorylation levels of AKT and key kinases in the Janus‐activated kinase (JAK)/signal transducer and activator of transcription‐3 (STAT3) pathway were detected by Western blot analysis. ATB overexpression promoted proliferation, migration, and invasion of A549 cells. Meanwhile, EMT of A549 cells was also enhanced. ATB silence showed the opposite influence. Expression of miR‐494 was negatively regulated by ATB. Following experiments showed ATB‐induced alterations of proliferation, migration, invasion, and EMT were all reversed by miR‐494 overexpression. Finally, we proved that ATB increased phosphorylated levels of AKT, JAK1, and STAT3, and those increases were all reversed by miR‐494 overexpression. We interestingly figured out that ATB promoted proliferation, migration, invasion, and EMT through down‐regulating miR‐494 in A549 cells. Moreover, ATB might activate AKT and the JAK/STAT3 pathway via down‐regulating miR‐494.
On the sensitivity of distributed acoustic sensing.

In distributed acoustic sensing (DAS) an optical fiber is transformed into an array of thousands of "virtual microphones. " Most current DAS methodologies are based on coherent interference of Rayleigh backscattered light and thus are prone to signal fading. Hence, the sensitivities of the "microphones" fluctuate randomly along the fiber. Therefore, specifying the sensitivity of DAS without considering its random nature is incomplete and of limited value. In this Letter, the statistical properties of DAS SNR and DAS sensitivity are studied in detail for the first time, to the best of our knowledge. It is shown that the mean dynamic DAS SNR is proportional to the SNR obtained in a single measurement of the fiber's "static" backscatter profile and, in turn, to the energy of the interrogation pulse. Finally, the minimum input signal, which produces a specified mean DAS SNR, is proposed as a new figure of merit for the characterization of system performances and for comparison between the sensitivities of different DAS modalities.
Anti-agrin autoantibodies in myasthenia gravis

Objective: Because the extracellular matrix protein agrin is essential for neuromuscular junction formation and maintenance, we tested the hypothesis that autoantibodies against agrin are present in sera from patients with myasthenia gravis (MG). Methods: We determined the presence of anti-agrin antibodies in 54 sera from patients with generalized MG using a solid-phase ELISA with purified mini-agrin protein. Thirty of the 54 sera were seronegative for antibodies against the acetylcholine receptor (AChR) or muscle-specific tyrosine kinase (MuSK), 15 had elevated levels of anti-MuSK, and 9 had elevated levels of anti-AChR autoantibodies. Sixteen sera from healthy volunteers served as control. Results: Five sera with elevated levels of anti-agrin antibodies were identified. The concentration of the antibodies ranged between 0.04 and 0.12 nM. Four of the 5 agrin-positive sera were also positive for anti-MuSK, one was positive for anti-AChR, and 2 had elevated levels of anti–low-density lipoprotein receptor-related protein 4 (LRP4) autoantibodies. Some of the sera stained adult mouse neuromuscular junctions and reacted with native mini-agrin expressed in 293HEK cells. Conclusions: The results provide evidence for agrin as a novel target protein for autoantibodies in patients with MG. Anti-agrin antibodies were always detected in combination with autoantibodies against MuSK, LRP4, or AChRs, indicating a high incidence of autoantibodies against several neuromuscular proteins in the agrin-positive MG cases.
BRD4 Regulates EZH2 Transcription through Upregulation of C-MYC and Represents a Novel Therapeutic Target in Bladder Cancer

People who develop bladder cancer frequently succumb to the intractable disease. Current treatment strategies are limited presumably due to the underlying molecular complexity and insufficient comprehension. Therefore, exploration of new therapeutic targets in bladder cancer remains necessary. Here, we identify that bromodomain-4 protein (BRD4), an important epigenome reader of bromodomain and extraterminal domain (BET) family member, is a key upstream regulator of enhancer of zeste homologue 2 (EZH2), and represents a novel therapeutic target in bladder cancer. We found that BRD4 was significantly overexpressed in bladder cancer cells and tissues. Inhibition of BRD4 decreased bladder cancer cell proliferation concomitantly with the accumulation of cell apoptosis in vitro and suppressed tumor growth in vivo. We further found that suppression of BRD4 decreased the mRNA and protein levels of EZH2, which was reversed by ectopic expression of C-MYC. In particular, individual silencing of BRD4 using shRNA or the BET inhibitor JQ1 strikingly diminished the recruitment of C-MYC to EZH2 promoter in bladder cancer. Briefly, our research reveals that BRD4 positively regulates EZH2 transcription through upregulation of C-MYC, and is a novel promising target for pharmacologic treatment in transcriptional program intervention against this intractable disease. Mol Cancer Ther; 15(5); 1029–42. ©2016 AACR.
Inhibitory Effect of Somatostatin on Cholecystokinin Release Is Independent of Luminal Cholecystokinin-Releasing Factor Content in Conscious Rats

Introduction Exclusion of bile–pancreatic juice from the intestine increases pancreatic secretion via cholecystokinin (CCK) release in conscious rats. Luminal CCK-releasing factor (LCRF), purified from rat intestinal secretions, is an intraluminal regulator of CCK secretion during bile–pancreatic juice diversion. Aims Because somatostatin is a potent inhibitor of CCK release and pancreatic secretion, the inhibitory effect of somatostatin on LCRF was examined. Methodology Rats were prepared with bile and pancreatic cannulae and two duodenal cannulae and with an external jugular vein cannula. The experiments were conducted without anesthesia. After 1.5-hour basal collection of pancreatic juice with bile–pancreatic juice return, bile–pancreatic juice was diverted for 2 hours, during which time somatostatin (2, 10 nmol/kg/h) was infused intravenously. The rats were killed before and 1 and 2 hours after bile–pancreatic juice diversion. To examine the effect of luminal somatostatin, 50 or 200 nmol/kg/h of somatostatin was infused into the duodenum. The plasma CCK and luminal content of LCRF were measured by specific radioimmunoassays. Results Bile–pancreatic juice diversion significantly increased pancreatic secretion, plasma CCK, and LCRF levels. Intravenous infusion of somatostatin inhibited CCK release and pancreatic secretion, but not LCRF content. Luminal administration of somatostatin did not show any effect. Conclusion Inhibitory effect of circulating somatostatin on CCK release and pancreatic secretion is independent of LCRF content.
Identity Management: Worker Independence and Discrimination Against Gay Men

I build on a growing literature documenting wage differentials for gay men by showing that the wage differential gay men experience varies significantly across occupations with different levels of worker independence. The penalty is smallest in management and professional occupations, which involve a high level of worker independence. It is largest in service occupations, which include a lower level of independence. This distribution of earnings penalties is consistent with discrimination being the source of the gay wage penalty. The results support the conjecture that higher levels of independence allow gay men to more successfully manage the disclosure of sexual orientation and mediate the negative effects of discrimination. (JEL J3, J7, J15)
Constrained-stochastic excitation coding of speech at 4.8 kb/s

In the last few years, Code-Excited Linear Predictive (CELP) coding has emerged as the most prominent technique for digital speech communication at rates of 8 Kb/s and below, and it is now considered the best candidate coder for digital mobile telephony and secure speech communication. While the CELP coder is able to provide fairly good-quality speech at 8 Kb/s, its performance at 4.8 Kb/s is yet unsatisfactory for many applications. The novelty in the CELP coding concept, namely, the stochastic excitation of a linear filter, also constitutes a weakness of this method: the excitation contains a noisy component which does not contribute to the speech synthesis process and can not be completely removed by the filter. It is a common opinion among speech communication researchers that new forms of excitations need to be studied in order to improve the CELP performance at low bit rates.
Children's use of information in word learning

ABSTRACT Whenever children hear a novel word, the context supplies information about its meaning. One way children may cope with so much information is to use whatever seems to make sense, given their prior knowledge and beliefs, while ignoring or quickly forgetting the rest. This work examined if and how children's beliefs about word meanings may affect their use of contrastive linguistic information in the input in word learning. In Study 1, some 3- and 4-year-olds were introduced to a novel material or shape name and heard it contrasted with familiar words. Others merely heard the novel word used for referring to an object. These children were then tested to determine what they had learned about their new word meaning. In Study 2, another group of 3-and 4-year-olds were asked to name the materials and shapes used for introducing these novel terms. Children made use of linguistic contrast only in some situations. They benefited more when the novel term did not overlap much in denotation with any terms commonly known by 3-and 4-year-olds. These results suggest that children can use information in the input very efficiently in learning a term for an as-yet-unnamed category, but not in learning a term similar in denotation to a word they already know. Thus, the results are consistent with the claim that children believe every word has a unique denotation.
Ex Vivo‐Expanded Cynomolgus Macaque Regulatory T Cells Are Resistant to Alemtuzumab‐Mediated Cytotoxicity

Alemtuzumab (Campath‐1H) is a humanized monoclonal antibody (Ab) directed against CD52 that depletes lymphocytes and other leukocytes, mainly by complement‐dependent mechanisms. We investigated the influence of alemtuzumab (i) on ex vivo‐expanded cynomolgus monkey regulatory T cells (Treg) generated for prospective use in adoptive cell therapy and (ii) on naturally occurring Treg following alemtuzumab infusion. Treg were isolated from PBMC and lymph nodes and expanded for two rounds. CD52 expression, binding of alemtuzumab and both complement‐mediated killing and Ab‐dependent cell‐mediated cytotoxicity (ADCC) were compared between freshly isolated and expanded Treg and effector T cells. Monkeys undergoing allogeneic heart transplantation given alemtuzumab were monitored for Treg and serum alemtuzumab activity. Ex vivo‐expanded Treg showed progressive downregulation of CD52 expression, absence of alemtuzumab binding, minimal change in complement inhibitory protein (CD46) expression and no complement‐dependent killing or ADCC. Infusion of alemtuzumab caused potent depletion of all lymphocytes, but a transient increase in the incidence of circulating Treg. After infusion of alemtuzumab, monkey serum killed fresh PBMC, but not expanded Treg. Thus, expanded cynomolgus monkey Treg are resistant to alemtuzumab‐mediated, complement‐dependent cytotoxicity. Furthermore, our data suggest that these expanded monkey Treg can be infused into graft recipients given alemtuzumab without risk of complement‐mediated killing.
Determinants of profitability of financial institutions in Latin America and the Caribbean

The Caribbean and Latin American countries are often treated as a single homogenous bloc. This frequently results in similar policy prescriptions for both regions—this can be problematic if the two regions are not in fact homogenous. First, the paper investigates if the characteristics of financial institutions (FI) in the Caribbean countries are different from their Latin American counterparts. Second, the paper delves into the relationships between the source of revenues and balance sheet composition, the profitability of these deposit taking financial institutions, and changes in the internal and external environments, by exploring the following research questions: (i) Do differences in the internal and external environments in which the FI operate affect its profitability? (ii) Do changes in the composition of revenues and balance sheet impact the FIs’ profits? This paper utilizes financial statement data and proxy variables that measure the internal structure from the Bankscope database of over 400 deposit taking financial institutions in the Caribbean region from 1998–2013. Macroeconomic data (measuring the external environment) were obtained from the World Bank’s World Development Indictors database. The dataset was organized as panel data with the stratification variable as the financial institution. Multiple regressions with fixed and random effects are used to determine how profitability, as measured by return on assets and return on equity, is impacted by the institution’s sources of revenues and expenses, its balance sheet composition, and its internal and external environments. Descriptive data showed that Caribbean financial institutions are smaller, less profitable, but have lower nonperforming loans than their Latin American counterparts. Profitability varied with the internal structure of the institutions, the external environment, and during the period prior to 2007, which was recorded as the most profitable years. Further analysis revealed that balance sheet composition and sources of revenues (and expenses) were highly significant in explaining differences in the institutions’ profitability. Specifically, profitability, as measured by return on equity and return on assets, is higher for financial institutions (i) that engage in nontraditional banking activities and (ii) that operate in less stable macroeconomic environments (higher inflation rates and depreciating currencies). The major implication from this study is that the ability of these financial institutions to achieve greater profitability is dependent on factors that are primarily within their control and not because they are significantly constrained by their external environment. Thus, banking regulators should focus on managerial capabilities in maintaining the institutions’ profitability to ensure safety and soundness in the financial system.