Miracle-dz/UniFAR-FTUs huggingface dataset:
DNA Methyltransferase 1 Is Indispensable for Development of the Hippocampal Dentate Gyrus

Development of the hippocampal dentate gyrus (DG) in the mammalian brain is achieved through multiple processes during late embryonic and postnatal stages, with each developmental step being strictly governed by extracellular cues and intracellular mechanisms. Here, we show that the maintenance DNA methyltransferase 1 (Dnmt1) is critical for development of the DG in the mouse. Deletion of Dnmt1 in neural stem cells (NSCs) at the beginning of DG development led to a smaller size of the granule cell layer in the DG. NSCs lacking Dnmt1 failed to establish proper radial processes or to migrate into the subgranular zone, resulting in aberrant neuronal production in the molecular layer of the DG and a reduction of integrated neurons in the granule cell layer. Interestingly, prenatal deletion of Dnmt1 in NSCs affected not only the developmental progression of the DG but also the properties of NSCs maintained into adulthood: Dnmt1-deficient NSCs displayed impaired neurogenic ability and proliferation. We also found that Dnmt1 deficiency in NSCs decreased the expression of Reelin signaling components in the developing DG and increased that of the cell cycle inhibitors p21 and p57 in the adult DG. Together, these findings led us to propose that Dnmt1 functions as a key regulator to ensure the proper development of the DG, as well as the proper status of NSCs maintained into adulthood, by modulating extracellular signaling and intracellular mechanisms. SIGNIFICANCE STATEMENT Here, we provide evidence that Dnmt1 is required for the proper development of the hippocampal dentate gyrus (DG). Deletion of Dnmt1 in neural stem cells (NSCs) at an early stage of DG development impaired the ability of NSCs to establish secondary radial glial scaffolds and to migrate into the subgranular zone of the DG, leading to aberrant neuronal production in the molecular layer, increased cell death, and decreased granule neuron production. Prenatal deletion of Dnmt1 in NSCs also induced defects in the proliferation and neurogenic ability of adult NSCs. Furthermore, we found that Dnmt1 regulates the expression of key extracellular signaling components during developmental stages while modulating intracellular mechanisms for proliferation and neuronal production of NSCs in the adult.
Global Warming Asset Pricing: Estimating a Temperature Risk Premium

This study considers the implications of long-term temperature risk in U.S. equity markets. Using raw temperature data, I create a proxy for low frequency temperature shocks and test for the existence of a priced temperature risk factor. I find no evidence supporting the existence of a cross-sectional temperature risk premium. Similarly, portfolios formed on low frequency temperature betas are not found to generate significant abnormal returns. Furthermore, industry temperature betas do not predict abnormal returns generated by the 2015 Paris Agreement, and firm temperature betas do not correlate with self-disclosed exposures to climate change risk. Overall, results provide no evidence of a priced low frequency temperature risk in U.S. markets. I attribute the lack of empirical results to the long time horizons of climate change induced disasters, investor diversification options and firm adaptability.
Genotypes and prevalence of HPV single and multiple concurrent infections in women with HSIL

The contribution of human papillomavirus (HPV) types to the carcinogenesis of cervical cancer has been established for a long time. However, the role of phylogenetically related and rare variants remains uncertain, as well as the influence of concurrent multiple HPV genotypes infection. We aimed at studying the prevalence of several HPV genotypes infecting women with single versus concurrent multiple HPV genotypes infection with a HSIL diagnosis in a cervical cytology. We conducted a cross‐sectional study using Thin‐Prep® liquid‐based cervical cytology specimens with the diagnosis of high‐grade squamous intraepithelial lesion (HSIL), in which HPV genotype was sequentially tested. Genotypes were determined with a PapilloCheck® system, a DNA‐Chip for the type‐specific identification of 18 high‐risk and six low‐risk types of HPV. Of the total study population, 176 cases had a diagnosis of HSIL and positive HPV genotyping result, being HPV16 the most prevalent genotype (48.86%; 95%CI: 41.58–56.19) followed by HPV31 (14.20%; 95%CI: 9.75–20.18). Concurrent multiple HPV genotypes were detected in 36.93% (95%CI: 30.15–44.27) of the patients. The prevalence of the 10 most common HPV genotypes detected varied significantly according to the presence of single vs. concurrent multiple HPV genotypes (P = 0.022). Moreover, women with concurrent multiple HPV genotypes were on average 3.53 (95%CI: 0.43–6.64) years younger than women with single genotype infection. Our results suggest that women with multiple genotype HPV infection differ in terms of age and distribution of the most prevalent HPV genotypes. Additionally, we provide further evidence of the predominance of HPV16 in HSIL lesions of the uterine cervix. Diagn. Cytopathol. 2014;42:919–923. © 2014 Wiley Periodicals, Inc.
The effects of temperament and behaviour problems on sedation failure in anxious children after midazolam premedication

Background and objective Midazolam is one of the most frequently used agents for sedation in paediatric dentistry. It is unclear how temperament traits and behaviour problems are related to sedation failure in children. We investigated whether sedation failure after premedication with oral midazolam can be predicted by behaviour problems and temperament traits. Methods Sixty children (aged 4–8 years) referred for dental treatment under sedation (40/60% N2O/O2), who had a Frankl Behaviour Scale score of at least 3, were premedicated with oral midazolam (0.75 mg kg−1). The level of sedation was assessed at defined time intervals, according to the Houpt Sedation Rating Scale. Children's sedation success during dental treatment was classified as satisfactory or unsatisfactory. Heart rate and oxygen saturation were evaluated by an oxygen saturation monitor in the sedation period. On the treatment day, parents completed ‘The Revised Conners’ Parent Rating Scale' and ‘Short Temperament Scale for Children’ to assess their child's behaviour problems and temperament, respectively. Results The rates of sedation success were found to be satisfactory in 78.4% and unsatisfactory in 21.6%. Student's t-test demonstrated that in addition to the Short Temperament Scale for Children Inflexibility subscale being significant the Revised Conners' Parent Rating Scale: Long Form Psychosomatic subscale was also found to be a significant predictor of sedation failure. Conclusion Psychosomatic behaviour problems and an inflexible temperament trait might contribute to sedation failure in children undergoing dental treatment under midazolam premedication and N2O/O2 sedation. Appropriate patient selection based on the evaluation of childhood behavioural problems and temperament characteristics might increase midazolam sedation success in children.
Clonal analysis of the origin of primordial germ cells in the mouse.

Qualitative and quantitative clonal analysis has been used to answer three basic questions about the establishment of the germ cell lineage in the mouse. Where do primordial germ cells originate? What is the size of the founding population at the time of lineage restriction? When and where does lineage restriction occur? Single epiblast cells of 6.0 dpc and 6.5 dpc mouse embryos were injected with a short-term lineage label (lysinated rhodamine dextran, LRDX) and their descendants traced after 40 h embryo culture at neural plate and early somite stages, respectively. An objective matching technique was used to detect the lineage marker in primordial germ cells identified by their characteristic alkaline phosphatase staining. Precursors of the primordial germ cells were found in the proximal epiblast close to the extraembryonic ectoderm in both pregastrulation and early-streak stage embryos. They form part of the presumptive extraembryonic mesoderm and are not lineage restricted while in the epiblast. Quantitative analysis gives a best fit to a model of a founding population of 45 at the time of lineage restriction. The data indicate that the generation time lengthens at the time of allocation. Calculation of clonal histories gives a best fit of 16 h generation time after allocation compared with < 7 h before allocation, with lineage restriction occurring at the early midstreak stage, presumably in the region posterior to the streak in which primordial germ cells are first identifiable. Therefore primordial germ cells are probably allocated early during gastrulation in a group of > 40 cells already segregated in the extraembryonic mesoderm.
Race and colorectal cancer screening: a population-based study in North Carolina.

OBJECTIVE National and state data document racial differences in colorectal cancer (CRC) mortality and incidence. Screening for CRC reduces cancer incidence and deaths. Racial differences in colorectal cancer screening behavior may contribute to the racial disparity in incidence and mortality. The purpose of this study was to determine if colorectal cancer screening rates are different between blacks and whites while controlling for potential confounders. STUDY DESIGN Cross-sectional survey. DATA SOURCE(S)/STUDY SETTING: We used data from the North Carolina Colon Cancer Study, a population-based case-control study conducted in 33 counties of North Carolina. We analyzed data from 598 control subjects who were eligible for colorectal cancer screening. METHODS Trained nurses conducted face-to-face interviews from October 1996 through October 2000. RESULTS Overall, 50% of the respondents were compliant with CRC screening guidelines. In the multivariable logistic regression model having a regular doctor and participation in a general medical exam were significantly associated with current screening status with odds ratios (OR) (95% confidence interval (CI)) of 3.8 (1.7-8.3) and 3.7 (2.1-6.7), respectively. Older age was a significant predictor of current screening status with an OR (95% CI) of 2.9 (1.7-4.8) for those 60-69 compared to respondents 50-59 and OR 3.2 (1.9-5.5) for those 70 and older compared to respondents 50-59. After adjusting for age, having a regular doctor and participation in general medical exams, race was not significantly associated with current CRC screening status, with an OR of 1.1 (95% CI 0.7-1.6). CONCLUSION CRC screening rates in North Carolina were low. Race was not a significant determinant of screening behavior and therefore does not explain the racial disparity in incidence or survival. Older age, having a regular doctor and participating in general medical exams were significant predictors of CRC screening. RELEVANCE This study reinforces the fact that screening rates in North Carolina are low despite the strong evidence that colorectal cancer screening reduces cancer deaths.
Morbidity following Prophylactic and Therapeutic Lymph Node Dissection for Melanoma - A Comparison

Between 1976 and 1982, 110 isolated regional lymph node dissections (RLND) for melanoma were performed as a prophylactic procedure (PLND) in 44 and therapeutic procedure (TLND) in 64 patients. The prevalence of metastases was 20 % in the PLND group. The number of patients with complications in the PLND were 17/44 (39 %) and in the TLND 39/64 (61 %). Local wound complications dominated. Serum collections occurred in 25 % of PLND patients and 45 % of TLND patients (p < 0.05), and infections, skin necrosis, and cellulitis in respectively 11 % and 22 %. The incidence of lymphedema was 10 % in PLND and 23 % in TLND patients. Regarding the anatomic sites, there were significantly more seromas after axillary dissection in TLND patients compared with PLND patients (p < 0.05). However, no difference was observed between groin dissections in the 2 groups. The socioeconomic effects in terms of hospital stay and further therapeutic measures were pronounced when complications occurred.
Predictive Factors for Early and Late Local Toxicities in Anal Cancer Treated by Radiotherapy in Combination With or Without Chemotherapy

BACKGROUND: The treatment of anal cancer is based on concomitant radiotherapy and chemotherapy and is associated with a nonnegligible rate of local severe toxicities that can strongly impair the quality of life. OBJECTIVE: A retrospective analysis was performed to screen the following factors as potential predictive factors for local skin and digestive toxicities, and as potential prognostic factors for cumulative colostomy incidence: sex, age, tumor size, clinical T and N stage, circumferential extension, invasion of anal margin, HIV status, type of chemotherapy, and type of radiotherapy and dose delivered. METHODS: One hundred five patients in our database treated between January 2000 and February 2010 met the eligibility criteria. RESULTS: Median follow-up was 54.1 months (range, 1–133). Early and late severe local toxicities occurred in 33 patients (31.4%) and 18 patients (17.1%). The 5-year cumulative rate of colostomy was 26.6%. Predictive factors for local severe early toxicities were as follows: clinical stage III/IV (p = 0.01), no brachytherapy boost (p = 0.003), and use of chemotherapy (p = 0.01). Only brachytherapy retained its independence in multivariate analysis (OR = 4.8 (1.4–16.3), p = 0.01). Human immunodeficiency virus positivity (p = 0.04) was the only predictive factor for late toxicities in univariate analysis; it was linked independently to the occurrence of ulcer (OR = 0.1 (0.01–0.66), p = 0.01). Tumor size ≥4 cm (p < 0.001) and occurrence of grade 2 to 3 ulcers (p < 0.001) were correlated with greater cumulative colostomy incidence. CONCLUSIONS: In this cohort, nonuse of brachytherapy was an independent predictive factor for local acute toxicity. Human immunodeficiency virus positivity was the only predictive factor for local late toxicities and strongly influenced the onset of ulcer.
LOCKING UP OUR OWN: CRIME AND PUNISHMENT IN BLACK AMERICA

Since Darren Wilson shot and killed Michael Brown in 2014,1 the problem of police violence against African Americans has been a relatively salient feature of nationwide discussions about race. Across the ideological spectrum, people have had to engage the question of whether, especially in the context of policing, it’s fair to say that black lives are undervalued. While there is both a racial and a political divide with respect to how Americans have thus far answered that question, the emergence of Black Lives Matter movements2 has made it virtually impossible to be a bystander in the debate. Separate from whether racialized policing against African Americans is, in fact, a social phenomenon, is the contestable question about solutions: Assuming that African Americans are indeed the victims of overpolicing, meaning that by some metric they end up having more interactions with the police and more violent encounters than is normatively warranted, what can we do about it? And here, the answers range from abolishing police officers altogether, to training them, to diversifying police departments. It is on the last of these proposed solutions — the diversification of police departments — that we focus in this essay. The central question we ask is: What are the dynamics that might shape how African American police officers police other African Americans? Asked another way, what do existing theories about race and race relations,
Immunosuppressive activity of capsaicinoids: capsiate derived from sweet peppers inhibits NF‐κB activation and is a potent antiinflammatory compound in vivo

Capsiate and its dihydroderivatives are the major capsaicinoids of sweet pepper. These new capsaicinoids do not activate the vanilloid receptor type 1 (VR1) but they share with capsaicin (CPS)some biological activities mediated in a VR1‐independent fashion. In this study we show that CPS and nordihydrocapsiate (CPT) inhibit early and late events in T cell activation, including CD69, CD25 and ICAM‐1 cell surface expression, progression to the S phase of the cell cycle and proliferation in response to TCR and CD28 co‐engagement. Moreover, both CPS and CPT inhibit NF‐κB activation in response to different agents including TNF‐α. CPS itself does not affect the DNA‐binding ability of NF‐κB but it prevents IκB kinase activation and IκBα degradation in a dose‐dependent manner, without inhibiting the activation of the mitogen‐activated protein kinases, p38, extracellular regulated kinase and c‐Jun N‐terminal protein kinase. Moreover, intraperitoneal pretreatment with CPT prevented mice from lethal septic shock induced by lipopolysaccharide. In a second model of inflammation CPT pretreatment greatly reduced the extensive damage in the glandular epithelium observed in the bowel of DSS‐treated mice. Taken together, these results suggest that CPT and related synthetic analogues target specific pathways involved in inflammation, and hold considerable potential for dietary health benefits as well as for pharmaceutical development.
Clinical Relevance of Intra-Abdominal Hypertension in Patients With Severe Acute Pancreatitis

Objectives: Intra-abdominal hypertension (IAH) contributes to organ failure in patients with abdominal trauma and sepsis and leads to the development of abdominal compartment syndrome (ACS). This study aims to investigate the clinical significance of IAH in patients with severe acute pancreatitis (SAP). Methods: Patients admitted to intensive care with SAP underwent daily measurement of intra-abdominal pressure (IAP), recording of the clinical data, and calculation of 4 organ dysfunction scores. Results: Among 18 patients with SAP, 11 (61%) developed IAH (median, 20 mm Hg), whereas 10 (56%) developed ACS. The IAP correlated significantly with the 4 organ dysfunction scores; the scores were significantly higher when IAH existed than when it did not. The admission IAP correlated significantly with the duration of intensive care stay. Patients who developed IAH/ACS had significantly higher organ failure score and greater mortality compared with those who did not. Laparotomy and drainage reduced the IAP by a median of −11 mm Hg and relieved the IAH/ACS in all patients. Conclusions: Intra-abdominal hypertension and ACS are frequent findings in patients with SAP and are associated with deterioration in organ function. Intra-abdominal pressure correlates with the severity of organ failure, and a high admission IAP is associated with prolonged intensive care stay.
Linear Time Memory Consistency Verification

Verifying the execution of a parallel program against a given memory consistency model (memory consistency verification) is a crucial problem in the functional validation of Chip Multiprocessor (CMP). In the absence of additional information, the above problem is known to be NP-hard. By adopting the pending period information, this paper proposes the first linear-time software-based approach to memory consistency verification. Our approach relies on a novel technique called reusable cycle checking, which reuses the previous order information when repeatedly checking cycle at different frontiers. In the context of pending period information, this technique significantly reduces the overall computational costs required by cycle checking, enabling linear-time (in the number of memory operations) memory consistency verification for any given multicore system with a constant number of processors. From a practical perspective, an industrial memory consistency verification tool, named XCHECK, has been developed based on our approach. XCHECK is capable of working with neither test program constraint nor dedicated hardware support in postsilicon verifications of many multiprocessor systems. Experimental results show that XCHECK is 3-10 times faster than a state-of-art software-based approach. XCHECK has been integrated into the verification platforms for an industrial multicore processor Godson-3B, and found several bugs of the design.
The determinants of urban sprawl: theory and estimation

ABSTRACT We argue that a well-articulated theory, by which we mean a set of structural equations equal in number to the endogenous variables and from which testable hypotheses may be drawn, should be the basis for any effort to estimate the determinants of urban sprawl. Without such a theory, it is not possible to know why a particular determinant ‘works’ to explain a particular definition of urban sprawl, nor is it possible to know whether any particular policy to combat sprawl, however defined, will be successful in achieving that objective without also creating other, possibly adverse, effects. To illustrate our argument, we contrast Burchfield, et al. [2006. Causes of sprawl: A portrait from space. The Quarterly Journal of Economics, 121, 587–633], which is not based on a well-articulated theory, with the urban monocentric model [Brueckner, 1987. The structure of urban equilibrium: A unified treatment of the Muth-Mills model. In E. S. Mills (Ed.), Handbook of regional and urban economics, Vol. II, “urban economics” (pp. 821–845). Amsterdam: Elsevier], which is a well-articulated theory.
Urinary obstruction in azotemic patients: detection by sonography.

Renal sonography is frequently requested in patients with an elevated or rising creatinine, often with the instruction to "rule out obstruction. " A prospective study of patients undergoing renal sonography for newly discovered azotemia (creatinine greater than 1.8 mg/dl) or worsening renal failure was undertaken to evaluate the clinical utility of the sonographic examination. Patients with known obstructive uropathy, renal calculi, renal mass, or hematuria were excluded. In 189 patients, 17 (9%) had hydronephrosis: 11 unilateral (one with a solitary kidney) and six bilateral. Obstructive causes were subsequently established in the solitary kidney and in four patients with bilateral dilatation. These five patients (2.6%) with clinically significant hydronephrosis were shown subsequently to have a clinical history that strongly suggested the presence of urinary tract obstruction. Our data suggest that, in patients without a clinical history that suggests obstruction (such as calculi, bladder outlet obstruction, or pelvic mass), the likelihood of finding bilateral hydronephrosis by sonography is small.
Pro‐inflammatory cytokines induce the transcription factors C/EBPβ and C/EBPδ in astrocytes

The transcription factors CCAAT/enhancer binding protein (C/EBP)‐β and ‐δ are key regulators for the expression of the acute phase genes in the liver, such as complement component C3 and antichymotrypsin. In the brain, these acute phase proteins are produced in response to pro‐inflammatory cytokines by the reactive astrocytes, in particular those surrounding the amyloid plaques of Alzheimer's disease brains. Here we show that lipopolysaccharides (LPS), IL‐1β, and TNFα induce the expression of the c/ebpβ and ‐δ genes in mouse primary astrocytes. This induction precedes the expression of the acute phase genes coding for the complement component C3 and the mouse homologue of antichymotrypsin. The induction of these two acute phase genes by LPS is blocked by cycloheximide, whereas this protein synthesis inhibitor does not affect the expression of the c/ebp genes. Altogether, our data support a role as immediate‐early genes for c/ebpβ and ‐δ, whose expression is induced by pro‐inflammatory cytokines in mouse cortical astrocytes. In the liver, these transcription factors are known to play an important role in inflammation and energy metabolism regulation. Therefore, C/EBPβ and ‐δ could be pivotal transcription factors involved in brain inflammation, in addition to their previously demonstrated role in brain glycogen metabolism regulation (Cardinaux and Magistretti. J Neurosci 16:919–929, 1996). GLIA 29:91–97, 2000. © 2000 Wiley‐Liss, Inc.