Miracle-dz/UniFAR-FTUs huggingface dataset:
Deletion mapping and X inactivation analysis of a non-specific mental retardation gene at Xp21.3–Xp22.11

We report on deletion mapping and X inactivation analysis of a gene for X linked non-specific mental retardation (MRX) at Xp21.3–Xp22.11, on the basis of molecular studies in two families with Xp microdeletions involving the DAX-1 gene. In family A, mental retardation (MR) was profound in the older brother with an episode of adrenal crisis, severe in the younger brother with no episode of adrenal crisis, and mild to moderate in the sister and the mother with no signs of adrenal hypoplasia. In family B, MR was absent in the male patient with adrenal hypoplasia. Polymerase chain reaction for 16 loci in the middle of Xp showed that the brothers of family A had a small Xp deletion between DXS7182 and DXS1022, and that the patient of family B had a tiny Xp deletion between DXS319 and DXS1022. Microsatellite analysis for tetranucleotide repeats in the promoter region of the DAX-1 gene and Southern blotting for DAX-1 and DXS28 showed that the sister and the mother of family A were heterozygous for the interstitial deletion. X inactivation analysis for the methylation status of the AR gene and the HPRT gene indicated that the normal X and the deleted X chromosome underwent random X inactivation in both the sister and the mother. The results imply that an MRX gene subject to X inactivation is present in a roughly 4 Mb region between DXS7182 and DAX-1, and that reduced expression of the normal MRX gene caused by random X inactivation results in MR in carrier females.
Methods for controller tuning for unstable systems

The paper deals with tuning of controllers for unstable plants. The controllers are presented for two types of plants: the unstable first order system and the unstable second order system, both with the uncertain plant gain. The control system design based on the algebraic approach using polynomials, the internal model control (IMC) structure and neuro-fuzzy inference system controller is used. The designed controllers are verified and compared by simulations on illustrative examples. The presented results show satisfactory control responses for the tracking of the step reference as well as for the step load disturbance attenuation.
[Peperphentonamine hydrochloride protects against gentamicin-induced cochlea damage by lowering cochlear caspase-3 expression in guinea pigs].

OBJECTIVE To study the protective effect of peperphentonamine hydrochloride (PPTA) against gentamicin-induced cochlear damage and its mechanism to inhibit cell apoptosis. METHODS Guinea pigs with normal hearing were randomized into control, gentamicin, and PPTA treatment groups, and the guinea pigs models of gentamicin-induced cochlear damage received intraperitoneal injection of PPTA. The changes of hearing of the guinea pigs were evaluated with auditory brainstem response (ABR) test, and the protein expression of caspase-3 in the cochlear tissue was detected using Western blotting. TUNEL staining, scanning and transmission electron microscopy were performed to observe the morphological changes of the cochlea. RESULTS The threshold in ABR in PPTA treatment group was significantly higher than that in the control group (P<0.05) but significantly lower than that in gentamicin group. Western blotting showed a significantly increased caspase-3 expression in gentamicin group (P<0.001); caspase-3 expression in PPTA group was obviously higher than that in the control group but much lower than that in gentamicin group (P<0.001). TUNEL assay and electron microscopy revealed serious damages of the hair cells in gentamicin group with numerous apoptotic cells in the organ of Corti, stria vascularis and spiral ganglion, and such cochlear damages were obviously alleviated in PPTA group. CONCLUSION PPTA can protect against gentamicin-induced cochlear damage in guinea pigs by decreasing the protein expression of caspase-3 to inhibit cell apoptosis.
Estrogen induces apoptosis in estrogen deprivation-resistant breast cancer through stress responses as identified by global gene expression across time

In laboratory studies, acquired resistance to long-term antihormonal therapy in breast cancer evolves through two phases over 5 y. Phase I develops within 1 y, and tumor growth occurs with either 17β-estradiol (E2) or tamoxifen. Phase II resistance develops after 5 y of therapy, and tamoxifen still stimulates growth; however, E2 paradoxically induces apoptosis. This finding is the basis for the clinical use of estrogen to treat advanced antihormone-resistant breast cancer. We interrogated E2-induced apoptosis by analysis of gene expression across time (2–96 h) in MCF-7 cell variants that were estrogen-dependent (WS8) or resistant to estrogen deprivation and refractory (2A) or sensitive (5C) to E2-induced apoptosis. We developed a method termed differential area under the curve analysis that identified genes uniquely regulated by E2 in 5C cells compared with both WS8 and 2A cells and hence, were associated with E2-induced apoptosis. Estrogen signaling, endoplasmic reticulum stress (ERS), and inflammatory response genes were overrepresented among the 5C-specific genes. The identified ERS genes indicated that E2 inhibited protein folding, translation, and fatty acid synthesis. Meanwhile, the ERS-associated apoptotic genes Bcl-2 interacting mediator of cell death (BIM; BCL2L11) and caspase-4 (CASP4), among others, were induced. Evaluation of a caspase peptide inhibitor panel showed that the CASP4 inhibitor z-LEVD-fmk was the most active at blocking E2-induced apoptosis. Furthermore, z-LEVD-fmk completely prevented poly (ADP-ribose) polymerase (PARP) cleavage, E2-inhibited growth, and apoptotic morphology. The up-regulated proinflammatory genes included IL, IFN, and arachidonic acid-related genes. Functional testing showed that arachidonic acid and E2 interacted to superadditively induce apoptosis. Therefore, these data indicate that E2 induced apoptosis through ERS and inflammatory responses in advanced antihormone-resistant breast cancer.
Direct evidence that sulfhydryl groups of Keap1 are the sensors regulating induction of phase 2 enzymes that protect against carcinogens and oxidants

Coordinate induction of phase 2 proteins and elevation of glutathione protect cells against the toxic and carcinogenic effects of electrophiles and oxidants. All inducers react covalently with thiols at rates that are closely related to their potencies. Inducers disrupt the cytoplasmic complex between the actin-bound protein Keap1 and the transcription factor Nrf2, thereby releasing Nrf2 to migrate to the nucleus where it activates the antioxidant response element (ARE) of phase 2 genes and accelerates their transcription. We cloned, overexpressed, and purified murine Keap1 and demonstrated on native gels the formation of complexes of Keap1 with the Neh2 domain of Nrf2 and their concentration-dependent disruption by inducers such as sulforaphane and bis(2-hydroxybenzylidene)acetone. The kinetics, stoichiometry, and order of reactivities of the most reactive of the 25 cysteine thiol groups of Keap1 have been determined by tritium incorporation from [3H]dexamethasone mesylate (an inducer and irreversible modifier of thiols) and by UV spectroscopy with sulforaphane, 2,2′-dipyridyl disulfide and 4,4′-dipyridyl disulfide (titrants of thiol groups), and two closely related Michael reaction acceptors [bis(2- and 4-hydroxybenzylidene)acetones] that differ 100-fold in inducer potency and the UV spectra of which are bleached by thiol addition. With large excesses of these reagents nearly all thiols of Keap1 react, but sequential reaction with three successive single equivalents (per cysteine residue) of dipyridyl disulfides revealed excellent agreement with pseudo-first order kinetics, rapid successive declines in reaction velocity, and the stoichiometric formation of two equivalents of thiopyridone per reacted cysteine. This finding suggests that reaction of cysteine thiols is followed by rapid formation of protein disulfide linkages. The most reactive residues of Keap1 (C257, C273, C288, and C297) were identified by mapping the dexamethasone-modified cysteines by mass spectrometry of tryptic peptides. These residues are located in the intervening region between BTB and Kelch repeat domains of Keap1 and probably are the direct sensors of inducers of the phase 2 system.
Continuous dopaminergic stimulation in early and advanced Parkinson’s disease

Evidence from preclinical and clinical studies indicates that pulsatile stimulation of striatal dopamine receptors is a key factor in the development of levodopa-associated motor complications. Therefore, in the de novo patient it is believed that providing a more continuous dopaminergic stimulation from the start of antiparkinson therapy may prevent priming for motor fluctuations and dyskinesia. Conversely, in the more advanced patient who is already suffering from motor complications, it is believed that providing a more continuous stimulation may reverse the development of motor complications, enabling the patient to enjoy more stable benefits from therapy. All PD patients eventually require levodopa therapy during the course of their disease, and the benefits of providing continuous dopaminergic stimulation with levodopa have been clearly demonstrated in a number of studies. However, these studies have included the use of approaches such as SC infusion or intra-intestinal infusion. Because these are relatively difficult to handle and not very practical for the patient, compliance is generally low. Therefore, the development of a simple treatment regimen using an oral formulation of levodopa to provide a more continuous dopaminergic stimulation will represent a significant advance in antiparkinsonian pharmacotherapy.
High-Fat, High-Sugar Diet Disrupts the Preovulatory Hormone Surge and Induces Cystic Ovaries in Cycling Female Rats

Diet-induced obesity has been associated with various metabolic and reproductive disorders, including polycystic ovary syndrome. However, the mechanisms by which obesity influences the reproductive system are still not fully known. Studies have suggested that impairments in hormone signaling are associated with the development of symptoms such as acyclicity and ovarian cysts. However, these studies have often failed to address how these hormonal changes arise and how they might contribute to the progression of reproductive diseases. In the present study, we used a high-fat, high-sugar (HFHS) diet to induce obesity in a female rodent model to determine the changes in critical reproductive hormones that might contribute to the development of irregular estrous cycling and reproductive cycle termination. The HFHS animals exhibited impaired estradiol, progesterone (P4), and luteinizing hormone (LH) surges before ovulation. The HFHS diet also resulted in altered basal levels of testosterone (T) and LH. Furthermore, alterations in the basal P4/T ratio correlated strongly with ovarian cyst formation in HFHS rats. Thus, this model provides a method to assess the underlying etiology of obesity-related reproductive dysfunction and to examine an acyclic reproductive phenotype as it develops.
Vascular biology of preeclampsia

Summary. Preeclampsia, a pregnancy‐specific syndrome characterized by hypertension, proteinuria and edema, resolves on delivery of the placenta. Normal pregnancy is itself characterized by systemic inflammation, oxidative stress and alterations in levels of angiogenic factors and vascular reactivity. This is exacerbated in preeclampsia with an associated breakdown of compensatory mechanisms, eventually leading to placental and vascular dysfunction. The underlying pathology of preeclampsia is thought to be a relatively hypoxic or ischemic placenta. Both the placenta and maternal vasculatures are major sources of reactive oxygen and nitrogen species which can interact to produce peroxynitrite a powerful prooxidant that covalently modifies proteins by nitration of tyrosine residues, to possibly alter vascular function in preeclampsia. The linkage between placental hypoxia and maternal vascular dysfunction has been proposed to be via placental syncytiotrophoblast basement membranes shed by the placenta or via angiogenic factors which include soluble flt1 and endoglin secreted by the placenta that bind vascular endothelial growth factor (VEGF) and placental growth factor (PIGF) in the maternal circulation. There is also abundant evidence of altered reactivity of the maternal and placental vasculature and of the altered production of autocoids in preeclampsia. The occurrence of preeclampsia is increased in women with preexisting vascular disease and confers a long‐term risk for development of cardiovascular disease. The vascular stress test of pregnancy thus identifies those women with a previously unrecognized at risk vascular system and promotes the development of preeclampsia. Preexisting maternal vascular dysfunction intensified by placental factors is possibly responsible for the individual pathologies of preeclampsia.
Genèse, situation actuelle et perspectives d'avenir des compagnies générales (Tông công Ty) en République socialiste du Vietnam à travers les sources vietnamiennes

La politique de reforme des entreprises d'Etat fut politiquement consacree en 1986, par la politique du Đồi moʾi. Desireux de mieux cerner le role, la nature, la structure de ces organisations dans le cadre de la reorganisation du secteur etatique au Vietnam, j'ai traite les informations en provenance de diverses sources ouvertes vietnamiennes, plus fournies, qui me permettaient de mieux apprehender la dimension politique et sociale que les autorites vietnamiennes souhaitaient faire jouer a ces entreprises, notamment les compagnies generales (Tổng cong ty). Heritee d'un systeme politique, placee au centre d'un processus global de transformation, la structure " compagnie generale " a du etre decrite et expliquee par les autorites aux differentes composantes de la societe vietnamienne. Ce travail de recherche, privilegie le traitement systematique de l'information ouverte vietnamienne pour permettre d'apprehender un sujet place dans une dynamique d'evolution determinee par les autorites vietnamiennes. Cette etude vise donc a presenter une structuration de la presse ecrite permettant de cerner le l'environnement et les techniques d'utilisation de l'information ouverte facilitant le traitement d'un sujet contemporain vietnamien. Ensuite nous tenterons de comprendre l'organisation et le role de ces compagnies dans le systeme vietnamien ; de souligner les premieres difficultes auxquelles sont confrontees ces structures (difficulte d'allier objectifs " socio politico-economiques " assignes et leur baisse de rentabilite economique sur des marches de moins en moins proteges) ; d'identifier les directions de reformes de ces structures preconisees par les autorites vietnamiennes dans le cadre de l'integration economique mondiale.
Guest Editor's Introduction: What is Infrastructure IP?

Every new node of semiconductor technology provides further miniaturization and higher performance, increasing the number of advanced functions that electronic products can offer. Although adding such advanced functions can benefit users, the manufacturing process is becoming finer and denser, making chips more susceptible to defects. Today’s very deep-submicron semiconductor technologies of 0.13 micron and below have reached susceptibility levels that put conventional semiconductor manufacturing at an impasse. These new defect levels require enhanced detection, test, diagnosis, and yield optimization solutions. Factory infrastructure (external equipment) alone is insufficient to handle such solutions; a supplemental on-chip support infrastructure is needed. To address this challenge, semiconductor IP providers have introduced embedded intellectual-property blocks, called infrastructure IP, and designers have incorporated these IP blocks into system-on-a-chip (SoC) designs. This D&T special issue covers a range of
Personal Factors Involved in Onset or Progression of Ménière’s Disease and Low-Tone Sensorineural Hearing Loss

Purpose: To identify personal causative factors for Ménière’s disease. Procedures: Patterns of hearing loss progression were studied in patients with Ménière’s disease and low-tone sensorineural hearing loss, and the involvement of stress and the relation of stressors to the onset or progression of the disease were analyzed. Results: Low-tone loss recurred in 40% of patients even after hearing was restored, and low-tone loss progressed to high-tone loss after frequent repetitions of recovery and recurrence. High-tone loss tended to proceed to all-tone loss. Eighty percent of patients reported that stress was involved or deeply involved in the onset or progression of the disease. Common causative stressors were business-related pressure, insufficient sleep, and troubles at the workplace or at home. Conclusions: The present findings indicate that recovery and recurrence may be influenced by the strength and duration of stress that is produced when patients do not feel rewarded for engrossment in their work or for self-inhibiting behaviors.
Effect of a novel beta-adrenoceptor agonist (Ro 40-2148) on resting energy expenditure in obese women.

The aim of this single-blind, placebo-controlled study was to investigate the effects of the new beta-adrenergic compound Ro 40-2148 on resting energy expenditure (REE) at rest and after an oral glucose load in non-diabetic obese women before and after two weeks of treatment. After one week of placebo administration and after an overnight fast and one hour rest, REE and glucose and lipid oxidation rates were measured by indirect calorimetry (hood system) before and for 6 h after a single dose of placebo solution. A 75 g oral glucose tolerance test (OGTT) was performed during this period starting 90 min after the placebo administration. During the following two weeks, using a randomization design, six patients received Ro 40-2148 at a dose of 400 mg diluted in 100 ml water twice a day (i.e. 800 mg per day), while six others continued with the placebo administration. The same tests and measurements were repeated after two weeks, except for the treatment group which received the drug instead of the placebo. The 14-day period of drug administration did not increase REE measured in post-absorptive conditions. Similarly, there was no acute effect on REE of a 400 mg dose of Ro 40-2148. In contrast, glucose-induced thermogenesis was significantly increased after two weeks in the treatment group (means +/- s.e.m.: 3.7 +/- 1.3%, P = 0.047), while no change was observed in the placebo group (-0.8 +/- 0.7%, not significant). Since there was no significant change in the respiratory quotient, the increase in energy expenditure observed in the treatment group was due to stimulation of both lipid and glucose oxidation. The drug induced no variations in heart rate, blood pressure, axillary temperature or in plasma glucose, insulin and free fatty acid levels. In conclusion, this study shows that Ro 40-2148 activates glucose-induced thermogenesis in obese non-diabetic patients.
Bone Loss Over 1 Year of Training and Competition in Female Cyclists

Objective:To observe changes in hip, spine, and tibia bone characteristics in female cyclists over the course of 1 year of training. Design:Prospective observational study. Setting:Laboratory. Participants:Female cyclists (n = 14) aged 26-41 years with at least 1 year of competition history and intent to compete in 10 or more races in the coming year. Assessment of Risk Factors:Women who train and compete in road cycling as their primary sport. Main Outcome Measures:Total body fat-free and fat mass and lumbar spine and proximal femur areal bone mineral density (aBMD) and bone mineral content (BMC) assessments by dual-energy x-ray absorptiometry. Volumetric BMD and BMC of the tibia were measured by peripheral quantitative computed tomography at sites corresponding to 4%, 38%, 66%, and 96% of tibia length. Time points were baseline and after 12 months of training and competition. Results:Weight and body composition did not change significantly over 12 months. Total hip aBMD and BMC decreased by −1.4% ± 1.9% and −2.1% ± 2.3% (P < 0.02) and subtrochanter aBMD and BMC decreased by −2.1% ± 2.0% and −3.3% ± 3.7% (P < 0.01). There was a significant decrease in lumbar spine BMC (−1.1% ± 1.9%; P = 0.03). There were no significant bone changes in the tibia (P > 0.11). Conclusions:Bone loss in female cyclists was site specific and similar in magnitude to losses previously reported in male cyclists. Research is needed to understand the mechanisms for bone loss in cyclists.
The Misuse of Spreadsheets in the Nuclear Fuel Industry: The Falsification of Safety Critical Nuclear Fuel Data Using Spreadsheets at British Nuclear Fuels Limited (BNFL)

This paper considers the management, technological and human factor issues that led to the BNFL fuel rod spreadsheet data falsification incident in 1999. BNFL discovered in 1999 that some data supporting quality assurance and safety processes had been falsified by BNFL workers using spreadsheets. The implication of this finding was that some of the Mixed Oxide Fuel Pellets shipped to customers in Japan for use in nuclear reactors were of an unknown mass and quality. This meant that the use of the MOX pellets fuel produced by BNFL would introduce uncontrolled factors into the safe operation of nuclear reactors. This could result in uncontrolled nuclear reactions and may have serious implications. The BNFL workers had cloned spreadsheets containing micrometer measurements and adjusted lot and batch numbers so that each spreadsheet appeared to be a genuine reflection of the quality and safety procedures put in place to ensure that the pellet dimensions, density and surface features are known and within acceptable tolerances. This paper will examine the production of MOX pellets at the Sellafield site, the falsification of data and the report commissioned by HM Nuclear Inspectorate. The paper will then identify a number of managerial and technological failings that led BNFL to use spreadsheets for recording such data.
On the theoretical basis of Carson's equations

In 1926 Carson produced his paper on ground return effects for overhead wires. It is surmised that the intended application of this work was telegraph circuits. The equations, however, have since been applied to transmission networks ranging from printed circuit boards to power systems. Carson in his derivation makes many assumptions, most of which are only alluded to. This makes defining the boundary conditions and consequently the scope of applicability for the work difficult. The basis for his work was an integral wave equation of general form, the derivation of which can be traced through later papers on the subject to a paper by Von Hoerschelmann. Efforts to obtain copy of Von Hoerschelmann's paper have made it apparent that this derivation is not available. This paper re-derives the wave equation of general form, details the assumptions used in derivation, compares them to what are believed to be Carson's assumptions and so defining the scope of Carson's equations.
DHEA. Monograph.

Dehydroepiandrosterone (DHEA) is a steroid hormone secreted primarily by the adrenal glands and to a lesser extent by the brain, skin, testes, and ovaries. It is the most abundant circulating steroid in humans and can be converted into other hormones, including estrogen and testosterone. It has been characterized as a pleiotropic "buffer hormone," with receptor sites in the liver, kidney, and testes, and has a key role in a wide range of physiological responses. Circulating levels of DHEA decline with age and a relationship has been suggested between lower DHEA levels and heart disease, cancer, diabetes, obesity, chronic fatigue syndrome, AIDS, and Alzheimer's disease. Other research suggests that autoimmune diseases such as systemic lupus erythematosus (SLE), rheumatoid arthritis, and multiple sclerosis might be associated with declining DHEA levels.