Miracle-dz/UniFAR-FTUs huggingface dataset:
Lipids and glucose in type 2 diabetes: what is the cause and effect?

Historically, type 2 diabetes was considered to revolve around a glucose-insulin axis. The foundations for this thinking were probably laid down by two momentous discoveries in diabetes research. According to popular legend, Oskar Minkowski noticed that urine from his pancreatectomized dogs attracted an inordinate number of flies. He is then alleged to have tasted the urine and noted its sweetness. From this observation came the supposition that the pancreas produced a substance that controlled sugar concentration, and diabetes occurred in the absence of this substance. The second landmark was the discovery by Frederick Banting that insulin was the active element from the pancreas. As a consequence of these two discoveries, the concept that the glucose-insulin relationship was the central element of fuel metabolism gained a firm hold. Diabetes has since been considered to be a disorder primarily associated with abnormal glucose metabolism. This notion is given credence by the considerable amount of data indicating that the chronic elevation of plasma glucose causes many of the microvascular complications of diabetes. In 1992, McGarry (1) asked what would have happened if Minkowski had lacked a sense of taste but had a good nose. If that had been the case, he may have smelled acetone, and this may have led him to the conclusion that removal of the pancreas affects fatty acid metabolism. If this had happened, our understanding of the pathogenesis of type 2 diabetes may have developed along a different route and led us more quickly to our current awareness that obesity, or more accurately, the products of excess adipose tissue, precede the perturbations of glucose metabolism. It is now apparent that elevation of plasma free fatty acids (FFAs) plays a pivotal role in the development of type 2 diabetes by causing insulin resistance. Type 2 diabetes develops because pancreatic β-cells …
A preliminary study of ritonavir, an inhibitor of HIV-1 protease, to treat HIV-1 infection.

BACKGROUND Ritonavir is a potent inhibitor in vitro of human immunodeficiency virus type 1 (HIV-1) protease, which is needed for virions to mature and become infective. We assessed the safety and efficacy of ritonavir in patients with HIV-1 infection. METHODS We administered ritonavir orally to 62 patients in one of four dosages during a 12-week trial containing a 4-week randomized, placebo-controlled, double-blinded phase followed by an 8-week dose-blinded phase. We assessed the response with serial measurements of plasma viremia and serial CD4 cell counts. RESULTS Fifty-two patients completed the 12-week trial. Diarrhea and nausea were the most common side effects, and reversible elevations in serum triglyceride and gamma-glutamyltransferase levels were the most frequent laboratory abnormalities. Ritonavir had a rapid antiviral effect, with a mean maximal reduction in the number of copies of HIV-1 RNA per milliliter of plasma that ranged from 0.86 to 1.18 log in the four dosage groups. After 12 weeks of treatment, the antiviral effect was partially maintained, with a mean reduction in plasma viremia of 0.5 log. When we used a more sensitive assay for HIV-1 RNA in a subgroup of 20 patients, we found that plasma viremia decreased by a mean of 1.7 log. This antiviral effect was partly sustained at week 12, with a mean reduction of approximately 1.1 log. The patients' CD4 cell counts rose during treatment with ritonavir (median increase, 74 and 83 cells per cubic millimeter at weeks 4 and 12, respectively). CONCLUSIONS The protease inhibitor ritonavir is well tolerated and has a potent antiviral effect, as shown by substantial decreases in plasma viremia and significant elevations in CD4 cell counts. Expanded clinical trials of ritonavir are warranted.
Propagation non-linéaire d'impulsions femtosecondes dans une fibre optique à bande interdite à cœur solide

Nous decrivons une etude experimentale et numerique de l'evolution non-lineaire d'impulsions ultrabreves se propageant dans une fibre optique a bande interdite a coeur solide. Suivant le mecanisme de guidage employe, des dynamiques significativement differentes sont mises en evidence.
Fibroblast Growth Factor Receptor Signaling Crosstalk in Skeletogenesis

Crosstalk of fibroblast growth factor signaling with other pathways may offer therapeutic strategies for skeletal dysplasias. Fibroblast growth factor receptor (FGFR) signaling controls a number of cellular processes. These functions are mediated by four FGFRs that are members of the receptor tyrosine kinase family. Studies of genetic models in mice and humans with FGFR mutations have provided evidence that inappropriate FGFR activity results in skeletal dysplasias. This Review, with three figures and 60 citations, describes the roles of FGFR signaling in determining skeletal cell fate and highlights how FGFR signaling cooperates with other signaling networks to control mesenchymal cell fate and differentiation. This crosstalk has important implications in potential treatment of skeletal disorders resulting from aberrant FGFR signaling. Fibroblast growth factors (FGFs) play important roles in the control of embryonic and postnatal skeletal development by activating signaling through FGF receptors (FGFRs). Germline gain-of-function mutations in FGFR constitutively activate FGFR signaling, causing chondrocyte and osteoblast dysfunctions that result in skeletal dysplasias. Crosstalk between the FGFR pathway and other signaling cascades controls skeletal precursor cell differentiation. Genetic analyses revealed that the interplay of WNT and FGFR1 determines the fate and differentiation of mesenchymal stem cells during mouse craniofacial skeletogenesis. Additionally, interactions between FGFR signaling and other receptor tyrosine kinase networks, such as those mediated by the epidermal growth factor receptor and platelet-derived growth factor receptor α, were associated with excessive osteoblast differentiation and bone formation in the human skeletal dysplasia called craniosynostosis, which is a disorder of skull development. We review the roles of FGFR signaling and its crosstalk with other pathways in controlling skeletal cell fate and discuss how this crosstalk could be pharmacologically targeted to correct the abnormal cell phenotype in skeletal dysplasias caused by aberrant FGFR signaling.
Memory retention of vestibuloocular reflex motor learning in squirrel monkeys

The vestibuloocular reflex (VOR) motor learning can be induced chronically by wearing lenses for several weeks to months, or acutely by visual-vestibular mismatch for several hours. Cerebellar long term depression (LTD) has been proposed as a causal mechanism for acute learning. We demonstrate differences in retention of acutely and chronically acquired VOR gains in squirrel monkeys and discuss neuronal correlates and possible roles of cerebellar LTD. Our data is compatible with the idea that cerebellar LTD might be a mechanism responsible for acute VOR adaptation.
PARAFILIAS, PEDOFILIA E INTERVENÇÕES EM TERAPIA COGNITIVO-COMPORTAMENTAL

A pratica da pedofilia e antiga e presente em varias culturas ao longo dos tempos, mas ainda pouco se tem pesquisado acerca de sua etiologia, e muito ainda se confunde pedofilia com abuso ou agressao sexual infantil, passivel mais de punicao pela justica do que tratamento clinico. O Brasil situa-se no ranking mundial de abusos sexuais de criancas e adolescentes. O objetivo deste artigo e apontar algumas reflexoes acerca dos conceitos de parafilia e pedofilia apos a publicacao do DSM-V , seu diagnostico e tratamento na atualidade. Dentre as estrategias de tratamento , a Terapia cognitivo-comportamental tem sido amplamente recomendada, justificando sua abordagem neste estudo. Palavras-chave: Pedofilia. Parafilia. Abuso Sexual Infantil. Terapia Cognitiva.
Sobre os Estados Emaranhados

O emaranhamento quântico esta na base de muitos estudos em computacao e informacao quânticas. Nesta comunicacao apresentamos alguns dados e conceitos relativos a este campo de pesquisa. Exemplos de estados emaranhados sao apresentados e seu uso em teletransporte quântico discutido.
Distinct and redundant roles of the two protein kinase A isoforms Tpk1p and Tpk2p in morphogenesis and growth of Candida albicans

TPK1 and TPK2 encode both isoforms of protein kinase A (PKA) catalytic subunits in Candida albicans. Mutants lacking both TPK1 alleles showed defective hyphal morphogenesis on solid inducing media, whereas in liquid hypha, formation was affected slightly. In contrast, tpk2 mutants were only partially morphogenesis defective on solid media, whereas a strong block was observed in liquid. In addition, the yeast forms of tpk2– but not tpk1– mutants were completely deficient in invading agar. Because Tpk1p and Tpk2p differ in their N‐terminal domains of approximately 80–90 amino acids, while the catalytic portions are highly homologous, the functions of hybrid Tpk proteins with exchanged N‐terminal domains were tested. The results demonstrate that the catalytic portions mediate Tpk protein specificities with regard to filamentation, whereas agar invasion is mediated by the N‐terminal domain of Tpk2p. Homozygous tpk1 and tpk2 mutants grew normally; however, a tpk2 mutant strain containing a single regulatable TPK1 allele (PCK1p‐TPK1) at low expression levels was severely growth defective. It was completely blocked in hyphal morphogenesis and was stress resistant to high osmolarities or temperatures. Thus, both Tpk isoforms in C. albicans share growth functions but, unlike Saccharomyces cerevisiae isoforms, they have positive, specific roles in filament formation in different environments.
Waveform design for high speed radar-communication integration

The integration of radar and communication is a good way to achieving miniaturization of the equipment, easing the tension of spectrum resource and reducing the interference between the radar and communication equipment. Recent research mainly concentrates on realizing the function of transmission and detection in one integrated equipment and improving the performance of radar with the random communication symbols, while improving the spectrum efficiency in communication is lack of study, which is also very important with the rapid growth of the need for multimedia transmission in either vehicular networking or battlefield. In this paper, based on multicarrier chirp signal (OFD-LFM), a spectrum effective integrated waveform with multiple symbols on each pulse is proposed and demodulation algorithm is work out. Simulation results show that optimal demodulation can be achieved simply by addition, subtraction and matching filtering, and the ambiguity function won't be influenced by the random communication symbols.
HBT Doherty amplifier using ballast resistor control and arbitrary termination impedance power divider

In this paper, a new HBT Doherty amplifier is designed with arbitrary termination impedance power divider and ballast resistor control method to enhance the dynamic gain flatness. By using the arbitrary termination impedance power divider, circuit size of the proposed HBT Doherty amplifier has been reduced considerably. Also, due to the fact that the gain of a peaking amplifier usually deteriorates the dynamic gain flatness of a Doherty amplifier, we proposed a novel technique of controlling ballast resistors according to the bias condition of a peaking amplifier. By tuning the ballast resistors and bias of peaking amplifier, we improved gain flatness of a Doherty amplifier maintaining permissible power added efficiency (PAE) at the same time. The proposed Doherty amplifier is designed at 1.9GHz with knowledge-on HBT process. Obtained the maximum power and the power gain through the simulation are 29dBm and 14.4dB, respectively. The PAE at the maximum output power was 64% with 3.3V supply voltage and achieved more than 60% over 5dB range.
Deletion of the PER3 gene on chromosome 1p36 in recurrent ER-positive breast cancer.

PURPOSE To investigate the role of the PER3 circadian rhythm gene, located within the commonly deleted region of chromosome 1p36, in human breast cancer development. PATIENTS AND METHODS The frequency of genetic alterations at 1p36 and PER3 gene copy number status were analyzed in 180 lymph node-negative breast cancers from patients who had received treatment with chemotherapy and/or tamoxifen. The expression levels of PER3 were also analyzed using published microarray profiles from > 400 breast cancer samples. Finally, the effect of loss of Per3 on tumor susceptibility was tested using two mouse models of breast cancer. RESULTS Deletion of PER3 is directly related to tumor recurrence in patients with estrogen receptor (ER) - positive breast cancers treated with tamoxifen. Low expression of PER3 mRNA is associated with poor prognosis, particularly in a subset of tumors that are ER positive, and either luminal A or ERBB2-positive tumors. Mice deficient in Per3 showed increased susceptibility to breast cancer induced by carcinogen treatment or by overexpression of Erbb2. CONCLUSION Disruption of PER3 function may serve as an indicator of probability of tumor recurrence in patients with ER-positive tumors. Further investigations of this pathway may reveal links between deregulation of sleep homeostasis and breast tumorigenesis.
A phase I trial of a yeast-based therapeutic cancer vaccine targeting CEA.

2604 Background: Saccharomyces cerevisiae (yeast) were engineered to express human CEA protein and administered as a heat killed, whole yeast therapeutic vaccine. Preclinical studies have shown that these modified yeast can induce a strong immune response to CEA as well as antitumor responses in a CEA-transgenic host. METHODS Patients (pts) were enrolled in this classic phase I design at 3 dose levels: 4, 16, and 40 yeast units (each unit =107 yeast particles). The vaccine was administered in equal doses at 4 sites subcutaneously in bilateral inguinal and anterior chest wall regions. Vaccine was administered at 2 week intervals for 3 months, then monthly. Eligible patients were required to have a serum CEA > 5 ng/ml or >20% CEA+ positive tumor block, ECOG PS 0-2, and no autoimmune history. An expansion cohort of 10 ECOG PS 0-1 pts was enrolled to focus primarily on immune response at the 40 yeast unit dose. Pts had re-staging scans at 3 months, then bimonthly. Peripheral blood was collected for analysis of immune response. RESULTS A total of 25 pts have enrolled. The most common adverse event (AE) is grade 1/2 site reaction (no grade ≥3 attributable AE). Most pts were heavily pre-treated with advanced disease where vaccine-induced immune response can be difficult to generate. Of 22 evaluable pts, 4 pts (3 colon and 1 medullary thyroid cancer) had stable disease beyond 3 months and 2 are on-going (3+, 5, 7, 8+). All 4 of these pts had declines or stabilization in serum CEA after treatment with vaccine was initiated. Immunologic analysis is ongoing. CONCLUSIONS A yeast-based vaccine targeting CEA has demonstrated safety and a subset of patients showed stable disease beyond 3 months. Immunologic activity is being evaluated and a study in medullary thyroid cancer pts with rising tumor markers is being planned.
Prospective study of urinary prostaglandin E2 metabolite and colorectal cancer risk.

PURPOSE Overexpression of cyclooxygenase-2 (COX-2) has been shown to play a major role in colorectal cancer pathogenesis. However, no human study has directly investigated whether biomarkers of COX-2 overexpression may predict colorectal cancer risk. We evaluated the association of urinary prostaglandin E2 metabolite (PGE-M) levels and colorectal cancer risk. METHODS A nested case-control study was conducted within the Shanghai Women's Health Study, in which 74,942 Chinese women ages 40 to 70 years were recruited from 1997 to 2000. Urinary PGE-M in 150 cohort members who developed colorectal cancer during the follow-up were compared with 150 matched controls. RESULTS The baseline level of urinary PGE-M was more than 50% higher in cases than in controls. The relative risks (RRs) of developing colorectal cancer were elevated from 1.0 to 2.5 (95% CI, 1.1 to 5.8), 4.5 (95% CI, 1.9 to 10.9), and 5.6 (95% CI, 2.4 to 13.5) with increasing quartiles of urinary PGE-M levels (P for trend < .001). The positive association was observed for both colon cancer (RR = 4.9; 95% CI, 1.7 to 14.7 for the highest v lowest quartile; P for trend = .009) and rectal cancer (RR = 7.2; 95% CI, 1.7 to 30.7; P for trend = .048), and for colorectal cancer cases diagnosed in the first 30 months (RR = 7.6; 95% CI, 1.8 to 32.0; P for trend = .035) and subsequent months (RR = 4.4, 95% CI, 1.5 to 13.3; P for trend = .012) of follow-up. CONCLUSION Given its strong association with colorectal cancer risk, urinary PGE-M may be a promising biomarker for risk assessment of this common malignancy.
LOOP: A Physical Artifact to Facilitate Seamless Interaction with Personal Data in Everyday Life

We investigated how a physical artifact could support seamless interaction with personal activity data in everyday life. We introduce LOOP (Figure 1), a physical artifact that changes its shape according to the activity data of the owner, providing an abstract visualization. This paper reports on the design process of LOOP that was informed by interviews and co-creation sessions with end users. We conclude with future work on the evaluation of the concept. This paper makes two main contributions. Firstly, LOOP is proposed as an example of an alternative approach to physically represent activity data. Secondly, the design process and rationale behind LOOP are presented as design knowledge.
Electric double-layer capacitors based on highly graphitized nanoporous carbons derived from ZIF-67.

Nanoporous carbons (NPCs) have large specific surface areas, good electrical and thermal conductivity, and both chemical and mechanical stability, which facilitate their use in energy storage device applications. In the present study, highly graphitized NPCs are synthesized by one-step direct carbonization of cobalt-containing zeolitic imidazolate framework-67 (ZIF-67). After chemical etching, the deposited Co content can be completely removed to prepare pure NPCs with high specific surface area, large pore volume, and intrinsic electrical conductivity (high content of sp(2) -bonded carbons). A detailed electrochemical study is performed using cyclic voltammetry and galvanostatic charge-discharge measurements. Our NPC is very promising for efficient electrodes for high-performance supercapacitor applications. A maximum specific capacitance of 238 F g(-1) is observed at a scan rate of 20 mV s(-1) . This value is very high compared to previous works on carbon-based electric double layer capacitors.
Theory of mind and the social brain: implications for understanding the genetic basis of schizophrenia

Genome‐wide association studies in schizophrenia have recently made significant progress in our understanding of the complex genetic architecture of this disorder. Many genetic loci have been identified and now require functional investigation. One approach involves studying their correlation with neuroimaging and neurocognitive endophenotypes. Theory of Mind (ToM) deficits are well established in schizophrenia and they appear to fulfill criteria for being considered an endophenotype. We aim to review the behavioral and neuroimaging‐based studies of ToM in schizophrenia, assess its suitability as an endophenotype, discuss current findings, and propose future research directions. Suitable research articles were sourced from a comprehensive literature search and from references identified through other studies. ToM deficits are repeatable, stable, and heritable: First‐episode patients, those in remission and unaffected relatives all show deficits. Activation and structural differences in brain regions believed important for ToM are also consistently reported in schizophrenia patients at all stages of illness, although no research to date has examined unaffected relatives. Studies using ToM as an endophenotype are providing interesting genetic associations with both single nucleotide polymorphisms (SNPs) and specific copy number variations (CNVs) such as the 22q11.2 deletion syndrome. We conclude that ToM is an important cognitive endophenotype for consideration in future studies addressing the complex genetic architecture of schizophrenia, and may help identify more homogeneous clinical sub‐types for further study
Inaccurate reaching associated with a superior parietal lobe tumor

A man with a tumor in the right superior parietal lobule had difficulty reaching for visualized objects. There were no significant deficits in visual sensation, visual attention, somatosensory function, elementary motility, praxis, or visuospatial performance. If allowed to visually fixate the target before reaching, he misreached only with his left arm and only when he was not allowed to observe the reaching limb. If he was required to maintain central visual fixation while reaching into his peripheral visual fields, his left arm misreached into both visual hemifields but his right arm misreached only into the left visual hemifield. These results demonstrate abnormalities, referable to both the contralateral arm and the contralateral visual field, that can neither be reduced to elementary disturbances of visual or somatosensory function nor to an elementary disturbance of motility. This pattern of misreaching has not been previously reported in human subjects or in experimental animals, but this may be attributable to differences of methodology. The misreaching observed in this patient may correspond to loss of posterior parietal neurons serving a supramodal integrative function.
New flicker weighting curves for different lamp types based on the lamp light spectrum

Flicker is a kind of annoyance of the human eyes. This is due to the fact that the human eyes are sensitive to the light color and light intensity, which vary under flicker conditions. The light color depends on the light spectrum. How the light spectrum varies under flicker is the interesting problem. In this paper, the lamp light spectrum of the incandescent lamp and the fluorescent lamp is presented. Based on the lamp light spectrum under flicker, a frequency domain flicker measurement proposal is described in this paper.
EVIDENCE BASED PUBLIC HEALTH POLICY AND PRACTICE Avoidable mortality by neighbourhood income in Canada: 25 years after the establishment of universal health insurance

Aim: To examine neighbourhood income differences in deaths amenable to medical care and public health over a 25-year period after the establishment of universal insurance for doctors and hospital services in Canada. Methods: Data for census metropolitan areas were obtained from the Canadian Mortality Database and population censuses for the years 1971, 1986, 1991 and 1996. Deaths amenable to medical care, amenable to public health, from ischaemic heart disease and from other causes were considered. Data on deaths were grouped into neighbourhood income quintiles on the basis of the census tract percentage of population below Canada’s low-income cut-offs. Results: From 1971 to 1996, differences between the richest and poorest quintiles in age-standardised expected years of life lost amenable to medical care decreased 60% (p,0.001) in men and 78% (p,0.001) in women, those amenable to public health increased 0.7% (p = 0.94) in men and 20% (p = 0.55) in women, those lost from ischaemic heart disease decreased 58% in men and 38% in women, and from other causes decreased 15% in men and 9% in women. Changes in the age-standardised expected years of life lost difference for deaths amenable to medical care were significantly larger than those for deaths amenable to public health or other causes for both men and women (p,0.001). Conclusions: Reductions in rates of deaths amenable to medical care made the largest contribution to narrowing socioeconomic mortality disparities. Continuing disparities in mortality from causes amenable to public health suggest that public health initiatives have a potentially important, but yet unrealised, role in further reducing mortality disparities in Canada.