Miracle-dz/UniFAR-FTUs huggingface dataset:
Full activation of p34CDC28 histone H1 kinase activity is unable to promote entry into mitosis in checkpoint-arrested cells of the yeast Saccharomyces cerevisiae

In most cells, mitosis is dependent upon completion of DNA replication. The feedback mechanisms that prevent entry into mitosis by cells with damaged or incompletely replicated DNA have been termed checkpoint controls. Studies with the fission yeast Schizosaccharomyces pombe and Xenopus egg extracts have shown that checkpoint controls prevent activation of the master regulatory protein kinase, p34cdc2, that normally triggers entry into mitosis. This is achieved through inhibitory phosphorylation of the Tyr-15 residue of p34cdc2. However, studies with the budding yeast Saccharomyces cerevisiae have shown that phosphorylation of this residue is not essential for checkpoint controls to prevent mitosis. We have investigated the basis for checkpoint controls in this organism and show that these controls can prevent entry into mitosis even in cells which have fully activated the cyclin B (Clb)-associated forms of the budding yeast homolog of p34cdc2, p34CDC28, as assayed by histone H1 kinase activity. However, the active complexes in checkpoint-arrested cells are smaller than those in cycling cells, suggesting that assembly of mitosis-inducing complexes requires additional steps following histone H1 kinase activation.
Head-shaking and Vibration-induced Nystagmus During and Between the Attacks of Unilateral Ménière’s Disease

Objective To aid in defining each phase of Ménière’s disease (MD) and underlying vestibular pathophysiology by analyzing the evolving patterns of spontaneous, head-shaking (HSN), and vibration-induced nystagmus (VIN) during and between the attacks of MD. Study Design Retrospective case series review. Methods We analyzed the patterns of HSN and VIN during 123 attacks from 87 patients who had definite unilateral MD and underwent recording of eye movements both during and between the attacks using video-oculography. Results HSN tended to beat toward the lesion side during the irritative phase (80.0%) and toward the healthy side during the paretic phase (82.9%). In contrast, VIN was more commonly induced during the irritative phase (63.7%) and more likely beat toward the healthy side irrespective of the phases evaluated (84.3%). Directional dissociation may occur between HSN and VIN, especially during the irritative phase when HSN mostly beat to the lesion side, but VIN is toward the healthy side. Conclusion The characteristic patterns of HSN and VIN during each phase of MD would aid in defining the acute phases of MD and understanding the underlying vestibular pathophysiology.
Ecthyma-like skin lesions caused by Staphylococcus aureus.

To the Editor. —Ecthyma gangrenosum is an uncommon but dramatic physical finding. It has been described as a classic sign ofPseudomonassepsis, but recent reports indicate that similar skin lesions may be produced byAeromonas hydrophila, lactosepositive vibrios, and perhaps other Gram-negative bacilli and fungi.1-3We would like to report the occurrence of necrotic skin lesions in two patients with systemicStaphylococcus aureusinfection. Both patients with hematologic malignant neoplasms were profoundly immunosuppressed and had skin lesions clinically indistinguishable from those described inPseudomonassepsis. Report of Cases. —Case 1. —A 68-year-old man with erythroleukemia and neutropenia was admitted to the hospital with acute onset of fever and dyspnea. Physical examination revealed a temperature of 38.9 °C, petechiae on the lower extremities, and three ecthyma-like lesions on the back and a forearm (Figure). The WBC count was 500/cu mm. Cultures of blood and skin lesions showed growth
Oestrogen treatment of experimental autoimmune encephalomyelitis requires 17β‐oestradiol‐receptor‐positive B cells that up‐regulate PD‐1 on CD4+ Foxp3+ regulatory T cells

It is now well accepted that sex hormones have immunoregulatory activity and may prevent exacerbations in multiple sclerosis during pregnancy. Our previous studies demonstrated that oestrogen (17β‐oestradiol; E2) protection against experimental autoimmune encephalomyelitis (EAE) is mediated mainly through oestrogen receptor‐α (ERα) and the membrane receptor G‐protein‐coupled receptor 30 (GPR30) and is abrogated in the absence of B cells and the co‐inhibitory receptor, Programmed Death‐1 (PD‐1). To critically evaluate the cell source of the E2 and PD‐1 co‐inhibitory pathways in EAE regulation, we assessed the requirement for ERs on transferred B cells and downstream effects on expression of PD‐1/PD‐ligand on CD4+ Foxp3+ regulatory T (Treg) cells in B‐cell‐replenished, E2‐treated B‐cell‐deficient (μMT−/−) mice with EAE. The results clearly demonstrated involvement of ERα and GPR30 on transferred B cells that mediated the protective E2 treatment effect on EAE and further showed an E2‐mediated B‐cell‐dependent up‐regulation of PD‐1 on CD4+ Foxp3+ Treg cells. These findings identify regulatory B‐cell populations as key players in potentiating Treg‐cell activity during E2‐mediated protection against EAE.
The problem-oriented record: a critique from a believer.

Abstract The problem-oriented medical record has been extensively described and widely recommended by many. Its true value in patient care, teaching, and clinical research must now be proved. Potential shortcomings of the system include overemphasis on style and compartmentalization, uncritical acceptance of a data base, inefficiencies in the process of data retrieval, lack of criteria for problem formulation, and an expectation that problem orientation alone will permit effective record auditing.
Synchronous Chemoradiotherapy in Patients with Stage III and IV Head and Neck Cancer: Comparing Cisplatin with Capecitabine

Purpose: To evaluate the efficacy of concurrent intravenous cisplatin versus oral capecitabine with radical radiotherapy in locally advanced squamous cell carcinoma of the head and neck. Materials and methods: Between January 2007 and December 2009, 60 patients with stage III/IV head and neck squamous cell carcinoma (0 to 1 performance status) were enrolled into this study. Thirty cases are given cisplatin 30 mg/m2 IV infusion weekly for 6 weeks with conventional radiotherapy. The remaining thirty cases are given oral capecitabine 500 mg/m2 twice daily, continuously for 28 - 35 days with conventional radiotherapy also. The radiotherapy dose was 4600 cGy in 20 fractions over 4 weeks to primary and neck nodes followed by boost to primary site and any residual disease 1500 - 2000 cGy in 6 to 8 fractions. Results: The median age was 53 (range 25 - 71) years; 10 cases had stage III disease, 36 cases IVa disease and 14 cases IVb disease. Seventy-three percent of patients completed the course of capecitabine and 80% completed prescribed cisplatin. There were no treatment-related deaths, grade 4 haematological toxicity or grade 3 renal toxicity in either arm. The complete response rate at 3 months was 77% (23/30 patients) in the capecitabine group and 60% (18/30) in the cisplatin group. Relapse occurred in 10/30 (33%) patients by 2 years in the capecitabine group and in 12/30 (40%) in the cisplatin group. On analysis of survival data, the median follow-up period was 35 ± 15 months for overall survival and 33 ± 10 months for disease free survival. The overall survival, and disease-free survival rates at 2 years were 67%, and 85%, respectively for the capecitabine group versus 60% and 73% for the cisplatin group. Conclusion: Synchronous chemo-radiotherapy with capecitabine was found to be very effective, with excellent response, local control and 3-year cancer-specific survival rates.
Relations between syntactic encoding and co-speech gestures: Implications for a model of speech and gesture production

Gestures that accompany speech are known to be tightly coupled with speech production. However little is known about the cognitive processes that underlie this link. Previous cross-linguistic research has provided preliminary evidence for online interaction between the two systems based on the systematic co-variation found between how different languages syntactically package Manner and Path information of a motion event and how gestures represent Manner and Path. Here we elaborate on this finding by testing whether speakers within the same language gesturally express Manner and Path differently according to their online choice of syntactic packaging of Manner and Path, or whether gestural expression is pre-determined by a habitual conceptual schema congruent with the linguistic typology. Typologically congruent and incongruent syntactic structures for expressing Manner and Path (i.e., in a single clause or multiple clauses) were elicited from English speakers. We found that gestural expressions were determined by the online choice of syntactic packaging rather than by a habitual conceptual schema. It is therefore concluded that speech and gesture production processes interface online at the conceptual planning phase. Implications of the findings for models of speech and gesture production are discussed.
Assessment of More Than 1,000 Implanted Percutaneous Bone Conduction Devices: Skin Reactions and Implant Survival

Objective This study assesses soft tissue reactions and implant stability of 1,132 percutaneous titanium implants (970 patients) for bone conduction devices (BCDs). In addition, it examines BCD usage and comparisons between different patient groups. Study Design Retrospective survey. Mean follow-up time of 4.6 years. Setting Tertiary care referral center. Patients The surveyed cohort was divided into 3 different age groups (children, adults, and the elderly). In addition, 4 groups with variable loading times (i.e., the time between placement of the implant and loading the BCD sound processor) were identified as well as a subgroup of patients with mental retardation. Main Outcome Measures Soft tissue reactions around the percutaneous implants as classified by the Holgers grading system, implant failure, and revision surgery rates. Results In 95.5% of the 7,415 observations of 1,132 implants, there were no adverse soft tissue reactions. Implant loss was 8.3%. Significantly more soft tissue reactions and implant failures were observed in children compared with adults and the elderly (p < 0.05). Implant survival was lower in patients with mental retardation compared with patients without mental retardation (p = 0.001). The loading time did not influence the occurrence of soft tissue reactions and implant survival rates. Conclusion Children and patients with mental retardation are the most vulnerable to soft tissue reactions and implant losses. Additional and more frequent care needs to be given during outpatient consultations. Because loading as early as 3 to 5 weeks did not negatively affect skin reactions or implant survival, full BCD installation can occur earlier without risk.
Secreting the Serine Protease HGF Activator in the Germinal Center Microenvironment by Hepatocyte Growth Factor (HGF) Activation Follicular Dendritic Cells Catalyze

Ag-speciﬁc B cell differentiation, the process that gives rise to plasma cells and memory B cells, involves the formation of germinal centers (GC). Within the GC microenvironment, multiple steps of B cell proliferation, selection, and maturation take place, which are controlled by the BCR in concert with cytokines and contact-dependent signals from follicular dendritic cells (FDCs) and T cells. Signaling by the multifunctional cytokine hepatocyte growth factor (HGF) and its receptor MET has been shown to induce integrin-mediated adhesion of B cells to VCAM-1, which is expressed by FDCs. In the present study we have examined the expression of regulatory components of the HGF/MET pathway, including HGF activator (HGFA), within the secondary lymphoid organ microenvironment. We show that MET is expressed by both centroblasts and plasma cells, and that HGFA is expressed by plasma cells. Because we have shown that HGF is a potent growth and survival factor for malignant plasma cells, HGF may also serve as a survival factor for normal plasma cells. Furthermore, we demonstrate that FDCs are the major source for HGF and its activator within the GC microenvironment. Both HGF and HGFA are expressed by FDCs in the GC dark zone (CD21 high / CD23 low ), but not in the light zone (CD21 high /CD23 high ). These ﬁndings suggest that HGF and HGFA provided by dark zone FDCs help to regulate the proliferation, survival, and/or adhesion of MET-positive centroblasts. The Journal of Immunology, 2005, 175: 2807–2813. HGFA in regulating HGF activation in normal lymphoid tissue. We demonstrate that HGFA is expressed by plasma cells, by other B-lineage populations. Furthermore, we show HGFA is strongly expressed by FDCs and is conﬁned to FDCs in the GC dark zone. These cells coexpress HGF and are in close contact with MET-positive centroblasts. Our ﬁndings suggest speciﬁc functions of the HGF/MET pathway in Ag-speciﬁc B cell differentiation, affecting plasma cell and centroblast functions.
Detection of Focal Liver Lesions with Superparamagnetic Iron Oxide: Value of STIR and SE Imaging

Objective We assessed the value of superparamagnetic iron oxide (SPIO) particles on the detection of focal liver lesions by MRI. Materials and Methods Twenty patients with one to five focal liver lesions, primarily detected with ultrasonography and/or contrast-enhanced CT, were evaluated further with unenhanced and iron oxide-enhanced MRI at 1.0 T. Superparamagnetic iron oxide particles were administered intravenously as a slow infusion. Then T1-, T2-, and proton density–weighted SE images were obtained. In addition, the performance of a short T1 inversion recovery (STIR) sequence was evaluated. Results The iron oxide contrast medium had marked effects on liver signal-to-noise (S/N) and tumor-to-liver contrast-to-noise (C/N) ratios but only minimal effects on tumor S/N ratios in cases of malignant tumor foci. Lesion-to-liver contrast, expressed as differences between the tumor and liver S/N ratios, improved very significantly after SPIO infusion with all four pulse sequences. Contrast enhancement of the liver parenchyma was best in T2-weighted SE images, but the tumor-to-liver C/N values were highest with the postcontrast STIR sequence. The SPIO enhancement revealed a number of additional focal lesions (31%), also foci under 1 cm in diameter. In three benign focal lesions, SPIO infusion produced a definite reduction in the S/N ratio of the lesions in contrast to the minimal change measured in malignant foci. The favorable performance of the STIR sequence contradicts the disappointing results previously obtained at 0.6 T. Conclusion Superparamagnetic iron oxide is a promising new contrast medium for MR examinations of the liver, increasing the conspicuity and reducing the detectability threshold of focal hepatic lesions.
Serum Malate Dehydrogenase as an Index of Placental Function

ES T I MAT ION of the functional capacity of the placenta remains one of the most important problems in obstetrics. Two main approaches have been made in recent times, both promising. In one, estimates are made of the output of various steroids but these methods are expensive, time consuming and demand a level of technical skill and equipment possessed by few laboratories. The second investigation has been concerned with the level of maternal blood enzymes associated with energy production on the assumption that there will be an upset in placental deficiency (Dawkins et al., 1959; Little, 1959; Heimback & Prezyna, 1960; Dawkins & Wigglesworth, 1961; Jeacock et al., 1962; Plauche & Mosey, 1962; Ricciardi et al., 1963 and others). Dawkins et al. (1959) and Jeacock et al. (1962) investigated the possible relationship of serum isocitric dehydrogenase (LCD) levels to placental degeneration in pre-eclampsia and found that correlation with clinical findings was not absolute. Little and Kirpalan (1962),however,noted a reduction in placental ICD in the presence of infarction and they concluded that in practice 'the ICD determination may ultimately prove useful in selectingpre-eclampsia cases for early delivery or for conservative therapy'. Studying enzymic histo-chemistry of the placenta Lobel et al. (1962) noted lactic dehydrogenase (LDH) conspicuously active in the trophoblast but levels of enzyme activity in the maternal circulation in pregnancy and pre-eclampsia were inconsistent (Stone et al.
Combinatorial issues in text-to-speech synthesis

Enhanced storage capacities and new learning algorithms have increased the role of text and speech training data bases in the construction of text-to-speech systems. It has become apparent, however, that not always learning algorithms are available that have strong generalization capabilities – the ability to generalize from cases seen in the training data base to new cases encountered during TTS operation. This makes it important to measure and understand the degree of coverage of the input domain of a text-to-speech system (usually, the entire language) by a given training data base. The goal of this paper is to investigate the feasibility of coverage in several domains of interest for TTS. It is shown that, as a result of the combinatorics of language, coverage is typically quite disappointing. This puts a premium on the generalization capability of learning algorithms.
Proactive spectrum sensing and spectrum sharing for cognitive radio.

Cognitive radio (CR) is emerging as a field essential to the progress of wireless communications. With spectral efficiency at the forefront in protocol design, CR aims in combating the supposed spectrum crisis due to inefficiency in spectral utilization. Thus a lot more spectrum-hungry services can be supported by the limited frequency bands through opportunistic access or sharing of licensed spectrum. As spectrum sensing precedes any possible access or sharing of spectrum, it is crucial that the sensing result is accurate when the initial sensing decision is made. Most of the current sensing techniques are passive in nature (i.e. they do not involve any participation of the CR) and hence can incur sensing errors when eavesdropping in the midst of high-noise or fading environments. Thus we consider a novel proactive spectrum sensing scheme that increases the certainty in the spectrum decision while combating the hidden-node problem. This is achieved when the CR sends out a probing signal prior to the sensing process. We study the results of applying power constraints to the power available for probing, and see how this scheme proves beneficial to the licensed user (LU) in terms of greater protection while still maintaining the throughput needs of the CR. After proactive sensing we focus our attention on the issues raised with spectrum sharing in the field of CR communication. As outlined by most work in literature, cross-channel estimation still remains an issue. Assumptions regarding cross-channel information are common amongst work that deals with a spectrum sharing protocol. In actuality this is impractical, and there is no way for the CR to ascertain the actual interference it deals to the LU. Thus we propose a supervised probing and sensing model that enables a CR to estimate the magnitude of the cross-channel link between itself and the LU, thus allowing for interference-shielding. With probing power playing an essential role in cross-channel estimation, we optimize the incremental probing step-size to allow for the highest estimation success and study its effect on cross-channel estimation error. Finally we take the conventional spectrum sharing protocols one step further to design proactive spectrum sharing. With a protocol established with bandwidth efficiency in mind, we see how cooperation
The role of institutions and health in European patterns of work and retirement

This article uses the Survey of Health, Ageing and Retirement in Europe (SHARE) to investigate the role of pension and social security institutions in shaping the European patterns of work and retirement. The key novelty of our article is a careful account of the health status of the respondents. We provide new evidence on the extent of health-adjusted ‘unused capacity’ in the labour force, on the institutional determinants of the pathways to retirement, and on the relationship between actual health status and disability-benefit recipiency. We find that institutional differences between countries explain much of the cross-national differences in work and retirement, while differences in health and demographics play only a minor role.
Expression of the apoptosis suppressing bcl‐2 protein in transitional cell bladder tumours

The expression of bcl‐2 protein was studied by immunohistochemistry using a monoclonal antibody in 158 cases of transitional cell bladder tumours. The bcl‐2 protein was expressed in basal cells in normal transitional epithelium and 68% of the transitional cell tumours showed bcl‐2 positivity in the basal cells. The expression of bcl‐2 in basal cells was positively correlated to over‐expression of epidermal growth factor receptor in tumour cells. The expression of bcl‐2 in non‐basal cells was weak in 20% and strong in an additional 13% of tumours. The expression of bcl‐2 in non‐basal cells was positively correlated to T‐category, M‐category, grade, papillary status, DNA ploidy, S phase fraction, mitotic index, nuclear area and over‐expression of epidermal growth factor receptor. Recurrence‐free interval of Ta‐T1 tumours was related to bcl‐2 positivity in non‐basal cells. Tumours with bcl‐2 positive non‐basal cells had an unfavourable prognosis but, in multivariate analysis, expression of bcl‐2 had no independent prognostic value.
Prospective Clinical Trial of Rifaximin Therapy for Patients With Primary Sclerosing Cholangitis

Primary sclerosing cholangitis (PSC) is a rare, chronic, cholestatic liver disease in which emerging data suggest that oral antibiotics may offer therapeutic effects. We enrolled patients with PSC in a 12-week, open-label pilot study to investigate the efficacy and safety of 550 mg of oral rifaximin twice daily. The primary end point was serum alkaline phosphatase (ALK) at 12 weeks. Secondary end points included (1) serum bilirubin, gamma-glutamyl transpeptidase, and Mayo PSC risk score; (2) fatigue impact scale, chronic liver disease questionnaire, and short form health survey (SF-36) scores; and (3) adverse effects (AEs). Analyses were performed with nonparametric tests. Sixteen patients were enrolled, among whom the median age was 40 years; 13 (81%) were male, 13 had inflammatory bowel disease, and baseline ALK was 342 IU/mL (interquartile range, 275–520 IU/mL). After 12 weeks of treatment, there were no significant changes in ALK (median increase of 0.9% to 345 IU/mL; P = 0.47) or any of the secondary biochemical end points (all P > 0.05). Similarly, there were no significant changes in fatigue impact scale, chronic liver disease questionnaire, or SF-36 scores (all P > 0.05). Three patients withdrew from the study due to AEs; 4 others reported mild AEs but completed the study. In conclusion, although some antibiotics may have promise in treating PSC, oral rifaximin, based on the results herein, seems inefficacious for this indication. Future studies are needed to understand how the antimicrobial spectra and other properties of antibiotics might determine their utility in treating PSC.
Nasal polyposis and its impact on quality of life: comparison between the effects of medical and surgical treatments

Background: Nasal polyposis (NP) is not a life‐threatening disorder but may have a great impact on the quality of life (QoL). The objective of this study: (i) to investigate the health burden incurred by NP compared with the Spanish general population using the Short Form‐36 Health Survey (SF‐36) questionnaire; (ii) to compare the QoL outcome after medical or surgical treatment; and (iii) to assess and compare the effect of medical and surgical treatment on nasal symptoms.