Miracle-dz/UniFAR-FTUs huggingface dataset:
CORRELATION OF FLEXION CONTRACTURES WITH UPPER EXTREMITY FUNCTION AND PAIN FOR SPINAL MUSCULAR ATROPHY AND CONGENITAL MYOPATHY PATIENTS

ABSTRACT To ascertain the patients' perception of the consequences of elbow flexion contractures and better understand the circumstances at their inception, we surveyed 405 spinal muscular atrophy and congenital myopathy patients. Diagrams of various elbow angles and questions concerning the effect of elbow contractures on daily activities were part of the survey. Of 108 completed responses, effectively a 24% response rate, 49 reported elbow flexion contractures. Thirteen of the 49 patients reported first noting them during extended periods of inactivity. Elbow flexion contractures greater than 25° were intractable and were reported to hamper 17% (77 of 410) of specifically considered daily activities for the 49 subjects. Twenty-nine of the 49 (59%) subjects with contractures complained of contracture-associated hindrance of at least one daily function. Perceived contracture-associated difficulties increased significantly as a function of contracture severity. Elbow contractures were perceived to be useful by 12% of the respondents. The correlation between contracture severity and upper limb discomfort was also striking. We conclude that elbow flexion contractures are common and perceived to be associated with disability and discomfort for about one-half of spinal muscular atrophy and congenital myopathy patients.
Elimination of Male Germ Cells in Transgenic Mice by the Diphtheria Toxin A Chain Gene Directed by the Histone H1t Promoter1

Abstract Expression of the diphtheria toxin A-chain gene was directed to the male germ line by fusion to 1 kilobase of the 5′-flanking DNA of the rat histone H1t gene. Two independent lines of mice were established that expressed the toxic transgene. Female carriers were fertile; males were sterile although otherwise apparently normal. Adult transgenic males had very small testes that were virtually devoid of germ cells. A developmental study showed that germ cells survived until late fetal life but that testes of 3-day-old transgenic mice were severely depleted of prospermatogonia. During postnatal development of transgenic animals, remaining germ cells progressed to the pachytene stage of meiosis in 10% to 30% of tubular cross sections but degenerated before the completion of meiosis. By 3 mo of age the residual germ cells had almost completely disappeared. These transgenic lines demonstrate the complete tissue specificity of the H1t promoter and reveal a period of its activity just prior to formation of the definitive adult spermatogonial stem cell population. Whereas full expression of H1t occurs only in mid to late pachytene spermatocytes, one or more of the factors that impart tissue specificity to its expression must be transiently activated in the neonatal germ line. This report discusses the possibility that this genetic technique for eliminating germ cells may have practical application in making recipients for spermatogonial stem cell transplantation.
DECLINE IN OFFSPRING VIABILITY AS A MANIFESTATION OF AGING IN DROSOPHILA MELANOGASTER

Abstract The evolutionary explanation of senescence proposes that selection against alleles with deleterious effects manifested only late in life is weak because most individuals die earlier for extrinsic reasons. This argument also applies to alleles whose deleterious effects are nongenetically transmitted from mother to progeny, that is, that affect the performance of progeny produced at late ages rather than of the aging individuals themselves. We studied the effect of maternal age on offspring viability (egg hatching success and larva-to-adult survival) in two sets of Drosophila melanogaster lines (HAM/LAM and YOUNG/OLD), originating from two long-term selection experiments. In each set, some lines (HAM and YOUNG, respectively) have been selected for early reproduction, whereas later reproduction was favored in their counterparts (LAM and OLD). In the HAM and LAM lines, both egg hatching success and larval viability declined with mother's age and did so with accelerating rates. The hatching success declined significantly faster with maternal age in HAM than in LAM lines, according to one of two statistical approaches used. Egg hatching success also declined with maternal age in YOUNG and OLD lines, with no difference between the selection regimes. However, the relationship between mother's age and offspring larva-to-adult viability differed significantly between these two selection regimes: a decline of larval viability with maternal age occurred in YOUNG lines but not in OLD lines. This suggests that the rate with which offspring viability declines with mother's age responded to selection for early versus late reproduction. We suggest broadening the evolutionary concept of senescence to include intrinsically caused declines in offspring quality with maternal age. Corresponding Editor: T. Mousseau
Presynaptic inhibition of the spinal monosynaptic reflex pathway

At present two distinct types of inhibition in the lumbosacral spinal cord of the cat are known. One type is effected by changes in the membrane potential (the inhibitory post-synaptic potential, IPSP) and in the excitability of the post-synaptic cell, and may, therefore, be referred to as postsynaptic inhibition. The characteristics of the IPSP have recently been reviewed (Eccles, 1957, 1961a, b; Kuffler, 1959; Frank & Fuortes, 1961). The second type of inhibition is characterized by a depression in the size of the excitatory post-synaptic potential (EPSP) without any detectable change in the resting membrane potential or in the excitability of the postsynaptic cell (Frank & Fuortes, 1957; Frank, 1959; Eccles, Eccles & Magni, 1960, 1961). Since there is evidence that the EPSP depression is a consequence of a depolarization of primary afferent fibres (Eccles, Eccles & Magni, 1961; Eccles, Magni & Willis, 1962; see also Eccles, 1961 a, b), this type of inhibition may be termed presynaptic inhibition. A convenient method of testing for inhibition in the spinal cord is to study the effect of conditioning volleys in various afferent nerve fibres upon the height of the monosynaptic reflex spike produced by a particular motor nucleus (Renshaw, 1942; Lloyd, 1946a, b; Laporte & Lloyd, 1952). The results of the present study show, by using this technique under conditions suitable for the production of presynaptic inhibition, that there is a powerful and prolonged depression of the monosynaptic reflex discharge; and arguments are presented that the reflex depression observed is due to presynaptic inhibition.
A phase II study of gefitinib in combination with FOLFOX-4 (IFOX) in patients with metastatic colorectal cancer.

3514 Background: Gefitinib (ZD1839, Iressa) is an inhibitor of epidermal growth factor receptor-1 and has been shown to produce growth inhibition and shrinkage in human tumors. Here we report the preliminary results of a trial to evaluate the efficacy and toxicity of Gefitinib (I) with FOLFOX-4 in patients (pts) with advanced colorectal cancer. METHODS Each cycle consisted of 14 days. Cycle 1 consisted of FOLFOX-4 while cycle 2 and subsequent cycles consisted of FOLFOX-4 with gefitinib at 500 mg PO qd. Pts were stratified by prior therapy for metastatic disease; Group A with no prior therapy and Group B with prior therapy Results: 56 pts have been enrolled (Group A: N=32; Group B: N=24) to date. Median age 54 years (range, 37-79) and median ECOG PS 0 (range 0-1). No patient had prior oxaliplatin. 359 cycles have been administered to date. All pts were assessable for toxicity and 49 were assessable for response. Two pts withdrew prior to completing 4 cycles due to unacceptable toxicity. Grade 3/4 toxicities included neutropenia (53%), diarrhea (49%), nausea (28%), and vomiting (21%). There was one treatment-related death (E. coli sepsis). In Group A, 21 of 27 pts (78%) achieved a partial response (PR). Nine patients in Group A went on to have liver metastases resected; only four of whom were deemed to have resectable disease at study entry. In Group B, 8 of 22 pts (36%) achieved PR. 18 of 22 Group B pts (82%) had received both Irinotecan and 5-FU. CONCLUSIONS Gefitinib with FOLFOX 4 represents an active regimen with response rates that are thus far encouraging compared with previously reported results using FOLFOX alone. Accrual continues to date. [Table: see text].
Mitogen-activated protein kinase ( MAPK ) pathway mediates the oestrogen-like activities of ginsenoside Rg 1 in human breast cancer ( MCF-7 ) cells

1Central Laboratory of the Institute of Molecular Technology for Drug Discovery and Synthesis, Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong SAR, China, 2State Key Laboratory of Chinese Medicine and Molecular Pharmacology, Shenzhen, China, 3Department of Physiology, Medical College of Qingdao University, Qingdao, China, and 4Shanghai Research Center for TCM Modernization, Shanghai Institute of Materia Medica, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China
A stimulation study of the dynamic power control method for VSCF doubly-fed induction wind turbine based on Labview

In wind power systems, wind turbine is a core component. The usual mathematical model of wind turbines are put forward under the circumstance of constant wind speed, that is, to study the characteristics of the active power and the slip ratio at a fixed rotor speed[1], but these models cannot fully describe the operation status of the wind turbines under actual circumstances; therefore, this paper endeavors to propose a mathematical model of wind turbine in the case of variable speed and achieve simulation system model through the Labview language. Based on this model, a dynamic power control strategy is further proposed and analyzed in theory. This theory lays a good foundation for the future design of dynamic power controller.
Efficacy, Safety, and Tolerability of the Cyclooxygenase-Inhibiting Nitric Oxide Donator Naproxcinod in Treating Osteoarthritis of the Hip or Knee

Objective. Naproxcinod, a cyclooxygenase-inhibiting nitric oxide donator antiinflammatory drug, was evaluated in this phase 2, double-blind, randomized, parallel group study to determine its optimal dose in patients with osteoarthritis (OA). Methods. In total 543 patients with OA of the hip or knee were randomized to receive naproxcinod 750 mg once daily (qd), 750 mg twice daily (bid), 1125 mg bid, rofecoxib 25 mg qd, or placebo for 6 weeks. The primary efficacy variable was the within-patient change from baseline to the average of Weeks 4 and 6 in WOMAC™ pain subscale score. Treatment-group differences were compared using ANCOVA with factors for treatment and country, and baseline pain subscale score as a covariate. Safety endpoints included vital signs and adverse events. Treatment-group differences in mean change from baseline to Week 6 in systolic blood pressure (SBP) were compared using an ANCOVA with treatment and country as fixed factors and baseline SBP as covariate. Results. All active treatments showed statistically significant reductions in WOMAC pain score compared to placebo (p ≤ 0.02). Naproxcinod was well tolerated. The 750 mg bid dose appeared to have the best balance of benefit versus safety. All 3 naproxcinod doses showed a reduction in SBP, while an increase was shown for rofecoxib. The changes for the naproxcinod groups were statistically significantly better compared to rofecoxib (p ≤ 0.02). Conclusion. This dose-finding study identified naproxcinod 750 mg bid as the upper dose for further therapeutic confirmatory clinical trials. Naproxcinod at all doses decreased mean SBP compared to an increase with rofecoxib.
Service chaining architectures for applications implementing distributed geographic information processing

Service-Oriented Architectures can be used as a framework for enabling distributed geographic information processing (DGIP). The Open Geospatial Consortium (OGC) has published several standards for services. These can be composed into service chains that support the execution of workflows constituting complex DGIP applications. In this paper, we introduce a basic architecture and building blocks for building DGIP applications based on service chains. We investigate the issues arising from the composition of OGC services into such service chains. We study various architectural patterns in order to guide application developers in their task of implementing DGIP applications based on service chains. More specifically, we focus on the control flow and data flow patterns in the execution of a workflow. These issues are illustrated with an example from the domain of risk management – a forest fire risk mapping scenario.
Ethnic differences in insulin sensitivity, β-cell function, and hepatic extraction between Japanese and Caucasians: a minimal model analysis.

CONTEXT Ethnic differences have previously been reported for type 2 diabetes. OBJECTIVE We aimed at assessing the potential differences between Caucasian and Japanese subjects ranging from normal glucose tolerance (NGT) to impaired glucose tolerance (IGT) and to type 2 diabetes. DESIGN This was a cross-sectional study with oral glucose tolerance tests to assess β-cell function, hepatic insulin extraction, and insulin sensitivity. PARTICIPANTS PARTICIPANTS included 120 Japanese and 150 Caucasian subjects. MAIN OUTCOMES Measures of β-cell function, hepatic extraction, and insulin sensitivity were assessed using C-peptide, glucose, and insulin minimal models. RESULTS Basal β-cell function (Φ(b)) was lower in Japanese compared with Caucasians (P < .01). In subjects with IGT, estimates of the dynamic (Φ(d)) and static (Φ(s)) β-cell responsiveness were significantly lower in the Japanese compared with Caucasians (P < .05). In contrast, values of insulin action showed higher sensitivity in the Japanese IGT subjects. Hepatic extraction was similar in NGT and IGT groups but higher in Japanese type 2 diabetic subjects (P < .01). Despite differences in insulin sensitivity, β-cell function, and hepatic extraction, the disposition indices were similar between the 2 ethnic groups at all glucose tolerance states. Furthermore, the overall insulin sensitivity and β-cell responsiveness for all glucose tolerance states were similar in Japanese and Caucasians after accounting for differences in body mass index. CONCLUSION Our study provides evidence for a similar ability of Japanese and Caucasians to compensate for increased insulin resistance.
Terror management in Japan

Do terror management effects generalize to non‐Western cultures? This question is significant because terror management theory offers an explanation of the origin of self‐esteem, whereas other research finds divergent self‐esteem motivations across cultures. The effects of mortality salience (MS) on the dual‐component anxiety buffer were investigated in Japan. A control group and a MS group were given an opportunity: (i) to defend their cultural worldview by derogating an anti‐Japan essay writer; and (ii) to boost their value within their cultures by indicating a greater desire for high‐status over low‐status products. Replicating past research with Western samples, Japanese in a MS condition were more critical of the anti‐Japan essay writer and they indicated a marginal tendency to prefer high‐ over low‐status products, compared with a control group. The theoretical implications are discussed.
The importance of the social and intellectual contexts in a discussion of the history of the concept of psychosis

Synopsis This paper shows that, throughout its 150 year history, the concept of ‘psychosis’ has not been static, but has reflected the intellectual and social contexts in which it has been employed. Initially the concept reflected the Romantic psychiatrists' emphasis on the whole personality. With the advent of materialism the concept was applied to all mental disorders. Because of the claims for organic cerebral findings in dementia praecox, it was described by Meyer as fitting the disease concept, with characteristic pathology, symptomatology, course and prognosis. However, the different social milieux of patients being treated by psychiatrists such as Kraepelin and Bonhoeffer led to different emphases regarding the aetiology of the psychoses. In the later twentieth century the influence of urbanization in Europe and Africa and also the rise of Nazism led to changes in relation to the use of the concept of psychosis.
The menarche experience in twenty-three foreign countries.

Ninety-five women (aged 18-26) from 23 countries were interviewed regarding their first menstrual experience. Among the areas discussed were (1) their preparation for menarche, (2) messages from others at the time of menarche, and (3) their own emotional reactions to the first period. Although the mother, as might be expected, was the main source of information, almost one-third of the girls received no maternal assistance prior to menarche. The chief reaction of others to a girl's first period centered on help with the hygienic routine. Only in Iran was a non-hygienic response more common--reassurance of the normality of the event. The emotional reactions of the women themselves differed widely. Asians most often reported feeling "embarrassed" and "surprised. " In contrast, Iranians most frequently mentioned feeling "more grown up". The discussion includes a comparison of the international women's descriptions of their menarche with data available on American samples. Finally, the paper concludes with an analysis of the importance of a culture's response to the menarcheal female.
Long‐term risks and benefits of a separate CSF access device with ventriculoperitoneal shunting in childhood hydrocephalus

To determine the long‐term risks and benefits of a separate CSF reservoir in the management of 52 children (23 males, 29 females) with shunted hydrocephalus, a retrospective study was performed comparing the use and complications after separate reservoir insertion, with a prereservoir control period. Median age at first shunt insertion was 1 month and median age at reservoir insertion was 2 years 6 months. Median follow‐up for shunt with the additional reservoir was 19 years 1 month. There was no mortality due to shunt failure nor CNS infection, and there were significantly fewer episodes of ventriculitis (p<0.01) and shunt blockage (p<0.0001) compared with the prereservoir period. There was no hemiplegia, epilepsy, visual, nor cognitive loss from the additional reservoir. The reservoir was used for access in 344 attendances (mean 6.62 attendances per patient) for diagnosis or treatment of raised pressure or CNS infection. It was concluded that a separate CSF reservoir is useful in the long‐term management of patients with shunted hydrocephalus and is without mortality or significant increased morbidity.
Place and Displacement: Towards a Distopological Approach

ABSTRACT Most recently, debates on decolonization, transformation, and Africanization raise, again, critical questions about the continuous dominance of the Western practice of philosophy in an African place. Such debates bear particular reference to colonization; however, they are relevant to any place where displacement is an issue and transformation demanded. Yet, the concept of displacement receives surprisingly little attention in these debates or in literature on place. I argue that place and displacement are inherently related, and explore some implications of this relation with regard to the practice of philosophy. My contention is that while displacement is an issue that raises specific challenges to the practice of Western philosophy in an African context, it is in fact a defining feature of philosophy as such in search of its place in the world. In conclusion, I propose what I call a distopological approach towards a philosophical practice that takes seriously its place and inherent relation to displacement.
Structure-Activity Relationships for Inhibition of Cysteine Protease Activity and Development of Plasmodium falciparum by Peptidyl Vinyl Sulfones

ABSTRACT The Plasmodium falciparum cysteine proteases falcipain-2 and falcipain-3 appear to be required for hemoglobin hydrolysis by intraerythrocytic malaria parasites. Previous studies showed that peptidyl vinyl sulfone inhibitors of falcipain-2 blocked the development of P. falciparum in culture and exerted antimalarial effects in vivo. We now report the structure-activity relationships for inhibition of falcipain-2, falcipain-3, and parasite development by 39 new vinyl sulfone, vinyl sulfonate ester, and vinyl sulfonamide cysteine protease inhibitors. Levels of inhibition of falcipain-2 and falcipain-3 were generally similar, and many potent compounds were identified. Optimal antimalarial compounds, which inhibited P. falciparum development at low nanomolar concentrations, were phenyl vinyl sulfones, vinyl sulfonate esters, and vinyl sulfonamides with P2 leucine moieties. Our results identify independent structural correlates of falcipain inhibition and antiparasitic activity and suggest that peptidyl vinyl sulfones have promise as antimalarial agents.
Low dose hypersensitivity following in vitro cell irradiation with charged particles: Is the mechanism the same as with X-ray radiation?

Abstract Purpose: Among the low dose effects that have been discovered during the past decade, the low dose hypersensitivity (HRS) is of prime importance. This phenomenon, compared to irradiation at higher doses used in conventional radiotherapy, enhances cell killing per unit dose at low doses and is followed by an induced radioresistance (IRR) effect. On survival fraction curves, a deviation from the linear quadratic model can be observed. HRS has mainly been studied after irradiation with sparsely ionizing radiation. Little work has been done to check its actual existence after irradiation with medium and high linear energy transfer (LET) particles. This article reviews recent studies involving HRS following irradiation of rodent and human cells with protons, alpha particles and carbon ions and assesses the applicability of a photon HRS model to charged particles. Conclusion: We propose that the HRS threshold dose and the radiosensitive parameter αs may be LET and deoxyribonucleic acid (DNA) damage-clustering dependent. Combining the use of high-LET particles at low doses and chemotherapy strategies increasing the proportion of HRS-sensitive cells could become a good candidate treatment for radioresistant cancers.