Miracle-dz/UniFAR-FTUs huggingface dataset:
Mimicking the action of folding chaperones in molecular dynamics simulations: Application to the refinement of homology‐based protein structures

A novel method for the refinement of misfolded protein structures is proposed in which the properties of the solvent environment are oscillated in order to mimic some aspects of the role of molecular chaperones play in protein folding in vivo. Specifically, the hydrophobicity of the solvent is cycled by repetitively altering the partial charges on solvent molecules (water) during a molecular dynamics simulation. During periods when the hydrophobicity of the solvent is increased, intramolecular hydrogen bonding and secondary structure formation are promoted. During periods of increased solvent polarity, poorly packed regions of secondary structures are destabilized, promoting structural rearrangement. By cycling between these two extremes, the aim is to minimize the formation of long‐lived intermediates. The approach has been applied to the refinement of structural models of three proteins generated by using the ROSETTA procedure for ab initio structure prediction. A significant improvement in the deviation of the model structures from the corresponding experimental structures was observed. Although preliminary, the results indicate computationally mimicking some functions of molecular chaperones in molecular dynamics simulations can promote the correct formation of secondary structure and thus be of general use in protein folding simulations and in the refinement of structural models of small‐ to medium‐size proteins.
Impact of the resin blood culture medium on the treatment of critically ill patients.

OBJECTIVE To assess the relevance, both clinical and bacteriologic, of the use of resin-containing blood culture media in blood cultures taken from critically ill patients receiving antibiotics. DESIGN A prospective, open clinical trial. SETTING The mixed medical surgical intensive care unit (ICU) of a 550-bed urban hospital. PATIENTS All ICU patients admitted during a 3-month period (n = 49) with suspected sepsis requiring blood cultures as part of their laboratory investigations. INTERVENTIONS The use of an aerobic resin-containing blood culture medium, in addition to the regular aerobic and anaerobic media for all blood cultures taken. MEASUREMENTS AND MAIN RESULTS Each blood culture result was classified as to its clinical significance. Changes in patient management were recorded. Culture sets in which the resin-containing bottle provided the information central to the change in patient management were identified. Bacteriologically, the results from the resin-containing medium were compared with the results from the aerobic and anaerobic media. Of 266 blood culture sets, 103 (39%) were positive, growing 278 bacterial and fungal isolates. Clinically, the resin-containing medium alone provided relevant data leading to changes in patient management on three occasions. On two of these occasions, cultures from the regular media provided the same data within 72 hrs. Bacteriologically, 77 (29%) aerobic bottles, 55 (21%) anaerobic bottles, and 89 (33%) resin-containing bottles were positive (statistical comparison of percentages: aerobic vs. resin-containing bottles, nonsignificant; aerobic vs anaerobic bottles, p < .046; anaerobic vs. resin-containing bottles, p < .0027). A similar proportion of pathogens was isolated from the resin-containing bottles only (9%) and aerobic bottles only (6%). A higher proportion of contaminants was isolated from the resin-containing bottles only than the aerobic bottles only in the various sets (17% vs. 7%, p < .046). The resin-containing bottle showed a trend toward increased detection of Staphylococcus aureus and Pseudomonas aeruginosa bacteremia. CONCLUSIONS The resin-containing medium offers little clinical benefit to the majority of ICU patients. Bacteriologically, it seems to have a similar overall sensitivity as the regular aerobic medium (with the possible exception of a higher sensitivity for the isolation of S. aureus and P. aeruginosa), but a lower specificity. The wide-spread use of the resin-containing bottle cannot be recommended.
Impedances for the Calculation of Electromagnetic Transients within Transformers

In this paper, a deep analysis of the behavior of transformer winding impedances for high frequencies is performed. The properties of inductance matrices are analyzed, as well as the possibility of making assumptions and their range of validity. The properties of resistance matrices are also analyzed, which has not been made in the past. The discussion on the influence of the iron core on inductance and resistance matrices is undertaken. The analysis is based on impedance measurements carried out on experimental transformer windings. Finally, recommendations are made about which are the most suitable impedance models for modeling transformers impedances during transient and resonance calculations.
Involvement of 5-methylcytosine in sunlight-induced mutagenesis.

In human skin cancers, more than 30 % of all mutations in the p53 gene are transitions at dipyrimidines within the sequence context CpG, i.e. 5'-TCG and 5'-CCG, found at several mutational hotspots. Since CpGs are methylated along the p53 gene, these mutations may be derived from solar UV-induced pyrimidine dimers forming at sequences that contain 5-methylcytosine. In Xorder to define the contribution of 5-methylcytosine to sunlight-induced mutations, we have used mouse fibroblasts containing the CpG-methylated lacI transgene as a mutational target. We sequenced 182 UVC (254 nm UV)-induced mutations and 170 mutations induced by a solar UV simulator, along with 75 mutations in untreated cells. Only a few of the mutations in untreated cells were transitions at dipyrimidines, but more than 95% of the UVC and solar irradiation-induced mutations were targeted to dipyrimidine sites, the majority being transitions. After UVC irradiation, 6% of the base substitutions were at dipyrimidines containing 5-methylcytosine and only 2.2% of all mutations were transitions within this sequence context. However, 24% of the solar light-induced mutations were at dipyrimidines that contain 5-methylcytosine and most of them were transitions. Two sunlight-induced mutational hotspots at methylated CpGs correlated with sequences that form the highest levels of cyclobutane pyrimidine dimers after irradiation with sunlight but not with UVC. The data indicate that dipyrimidines that contain 5-methylcytosine are preferential targets for sunlight-induced mutagenesis in cultured mammalian cells, thus explaining the large proportion of p53 mutations at such sites in skin tumors in vivo.
Pharmacological characterization of the metabotropic glutamate receptor inhibiting d‐[3H]‐aspartate output in rat striatum

1 The effects of several agonists of the metabotropic glutamate receptor (mGluR) were studied in adult rat striatal slices by measuring (i) KCl (30 mm)‐induced output of previously taken up d‐[3H]‐aspartate (Asp), (ii) forskolin (30 μm)‐induced adenosine 3′:5′‐cyclic monophosphate (cyclic AMP) accumulation and (iii) phophoinositide (PI) hydrolysis. 2 K+‐induced efflux of d‐[3H]‐Asp was inhibited by the following mGluR agonists: (1S,3S,4S)‐(carboxycyclopropyl)glycine (l‐CCG‐I), (1S,3R)‐1‐aminocyclopentane‐1,3‐dicarboxylic acid (1S,3R‐ACPD) and quisqualic acid (Quis). 2‐Amino‐4‐phosphonobutyrate (l‐AP4) was inactive up to 300 μm. The maximal inhibition of d‐[3H]‐Asp output was 60 ± 8%. The EC50s of mGluR agonists were: 0.5 μm for l‐CCG‐I, 100 μm for 1S,3R‐ACPD and 100 μm for Quis. 3 Forskolin‐induced cyclic AMP accumulation was also inhibited by mGluR agonists. The maximal inhibition was 50 ± 4% and was obtained at a concentration of 10 μm for l‐CCG‐I and 100 μm for 1S,3R‐ACPD. The EC50s for this inhibition were: 0.9 μm for l‐CCG‐I and 20 μm for 1S,3R‐ACPD. Quis (300 μm) inhibited cyclic AMP accumulation by approximately 20%. l‐AP4 slightly potentiated cyclic AMP accumulation. 4 PI hydrolysis was stimulated by mGluR agonists. The most potent compound was Quis (100 μm), which increased inositol phosphate formation up to 2.2 fold over control values. Its EC50 was 15 μm. l‐CCG‐I and 1S,3R‐ACPD increased inositol phosphate formation by approximately 1.8 fold and their EC50 values were 30 and 25 μm, respectively. l‐AP4 did not affect PI hydrolysis. 5 In conclusion, mGluR agonists that reduce d‐[3H]‐Asp output have a pharmacological profile similar to that of mGluR agonists inhibiting cyclic AMP accumulation. l‐CCG‐I appears to be a relatively selective agonist for the mGluR receptor which inhibits d‐[3H]‐Asp efflux and cyclic AMP accumulation, while Quis appears to act preferentially on the mGluR receptor linked to the metabolism of PIs.
Tensor Fasciae Latae Combined With Tangentially Split Vastus Lateralis Musculocutaneous Flap for the Reconstruction of Pressure Sores

Pressure sores in the ischial and the trochanteric regions are usually encountered in long-term bedridden and wheelchair-dependent patients. A number of techniques have been developed for the reconstruction of pressure sores. Tensor fasciae latae musculocutaneous flap has been extensively employed to close the trochanteric defect. Despite its utility of having a constant pedicle and proximal bulky muscle, the relative shortness of the flap and insufficient padding in the distal portion limit the applications for distant locations of pressure sores. From January 2001 to December 2003, 8 patients with ischial and trochanteric pressure sores underwent tensor fasciae latae reconstruction in combination with tangentially split vastus lateralis muscle. The descending branches of the lateral circumflex femoral arteries were also included in these flaps. All of the procedures have been successful, and no flap necrosis has been observed. Sufficient bulk of the flap and reliable distal skin paddle constitute the advantages of this flap.
Diagnosis, treatment and prognosis of the leiomyosarcoma of the inferior vena cava. Three cases and summary of published reports.

OBJECTIVE To describe our experience with three cases of leiomyosarcoma of the inferior vena cava, and summarise current methods of diagnosis and treatment. DESIGN Descriptive study. SETTING University hospital, Germany. SUBJECTS 3 Patients with histologically confirmed leiomyosarcoma of the inferior vena cava. INTERVENTIONS Resection, with or without vascular reconstruction. MAIN OUTCOME MEASURES Morbidity and mortality. RESULTS Case 1 was diagnosed on magnetic resonance imaging, the tumour was resected, and the vena cava replaced with a polytetrafluoroethylene (PTFE) graft. She made an uncomplicated recovery and was well and free of symptoms 10 months later. Case 2 was diagnosed at operation (the differential diagnosis on computed tomography was a retroperitoneal tumour), the tumour was resected, and the defect oversewn. She made an uneventful recovery and was well and free of symptoms 14 months later. Case 3 was diagnosed at operation (a diagnosis of pancreatic cancer had been made preoperatively), the tumour was resected, and the defect oversewn. She was well and free of symptoms 10 months after operation. CONCLUSIONS Magnetic resonance imaging is superior to computed tomography in the diagnosis of leiomyosarcoma of the inferior vena cava. The treatment of choice is resection; small defects can be closed by suture or PTFE patch, and large defects by PTFE prostheses. Reported resectability is 40% to 60%, but the prognosis is poor; the local recurrence rate is about 36%, most patients are dead within 2.5 years, and the 5-year survival is 30%. Chemotherapy and radiotherapy will give some degree of palliation, but do not affect the outcome.
Obsessive-compulsive symptoms during treatment with olanzapine and risperidone: a prospective study of 113 patients with recent-onset schizophrenia or related disorders.

OBJECTIVE To determine whether severity of obsessive-compulsive symptoms (OCS) differs during treatment with olanzapine or risperidone and to establish whether duration of antipsychotic treatment is related to severity of OCS. METHOD We conducted a prospective study of consecutively hospitalized young patients (mean age = 22.4 years) with DSM-IV schizophrenia or related disorders (N = 113) who were treated with olanzapine or risperidone. Olanzapine or risperidone was randomly prescribed for patients who were drug-naive or were treated with typical antipsychotics before admission (N = 36). Patients who had started olanzapine (N = 39) or risperidone treatment (N = 23) prior to admission continued with that medication if they showed initial clinical response. Patients who prior to admission started olanzapine (N = 6) or risperidone (N = 9) but showed no response or suffered from adverse effects switched at admission to risperidone or olanzapine, respectively. Medical records, parents, and patients revealed information on duration of treatment and compliance with olanzapine or risperidone prior to admission. The Yale-Brown Obsessive Compulsive Scale (YBOCS) was administered at admission and 6 weeks thereafter. RESULTS At baseline and 6-week assessments, OCS were found in about 30% of 106 evaluable cases and 15% met DSM-IV criteria for obsessive-compulsive disorder. No differences in OCS were found in the patients randomly assigned to olanzapine or risperidone. The 35 subjects treated with olanzapine at both assessments had significantly (p = .01) more severe OCS at week 6 than the 20 subjects treated with risperidone at both assessments. Duration of treatment with olanzapine was significantly (p < .01) related to severity of OCS. CONCLUSION There are no differences in the short-term propensity of olanzapine or risperidone to induce or exacerbate OCS. However, severity of OCS was associated with duration of treatment with olanzapine.
Diabetes prevention in a faith-based setting: results of translational research.

AIM The purpose of this study was to translate the National Institutes of Health (NIH)-Diabetes Prevention Program (DPP) into a church-based setting. METHODS The lifestyle arm of the NIH-DPP was implemented in an African American Baptist church. Church members 18 years or older completed a risk screen during Sunday service followed by fasting glucose (FG) testing at the church during the week. Persons with prediabetes participated in a 16-session DPP conducted over 4 months. Participation rates, height, weight, blood pressure (BP) and FG were followed for 12 months post-intervention. Fifty participants completed the risk screen, 26 were at risk for diabetes, 16 of 26 received FG testing, and 8 had prediabetes (FG = 100- 125 mg/dL). RESULTS The mean participation rate was 10.4 (65%) sessions. Following the intervention, weight, systolic and diastolic BP, and FG decreased by 7.5 lb (3.6%), 16 mm Hg (11.7%), 12 mm Hg (14.0%), and 5 mg/dL (4.8%), respectively (P < .05). In comparison with baseline, significant reductions were evident at 6 and 12 months postintervention for all endpoints. CONCLUSIONS This study demonstrated successful translation of the 16-session NIH-DPP into a church-based setting. Future studies should test this intervention in churches of different sizes and denominations.
Benefits versus risks from mammography: A critical reasessment

The use of mammography has increased rapidly over the last decade. The justification for mammographic examinations is the potential benefit they provide in detecting breast cancer at an early stage and reducing mortality. However, this benefit must be balanced against the associated potential risk of radiation carcinogenesis, economic costs, and a number of other factors. Most publications to date have used radiation risk factors and data from studies that were published over a decade ago, which now have been superseded by the results of more recent epidemiological studies.
Aurora‐B phosphorylates Histone H3 at serine28 with regard to the mitotic chromosome condensation

Background: Histone H3 (H3) phosphorylation plays important roles in mitotic chromosome condensation. We reported that H3 phosphorylation occurs at Ser28, as well as at Ser10 during mitosis, at least in mammals. Aurora B was recently demonstrated to be responsible for Ser10 phosphorylation in S. cerevisiae, C. elegans, Drosophila and Xenopus egg extract.
IDENTITY STYLES OF SOCIAL MEDIA AND NETWORK GAMES USERS

Period of emerging adulthood is a time of intense search for identity by young people who are building their concept of themselves mainly through three ways: a philosophical reflection, by shaping new social relations, and by professional activity [1]. The identity-building process can take different forms, which Berzonsky calls styles. These are the methods by which people construct and utilize their knowledge of decision making in everyday life [2]. The following are three styles of identity building: informative, normative and diffusion-avoidance. Information-style persons make independent efforts to search, process and evaluate information related to "I". People with a normative style more automatically internalize their knowledge and adjust to the expectations of significant individuals, authorities. The diffusion-avoidance style consists in shifting and avoiding as far as possible the conflicts and situations that force decisions [3]. In today's world thanks to the use of social media, young people have almost unlimited opportunity to interact with a variety of views and positions that are both similar and contradictory to their own. This is an opportunity to develop reflection on the concept of self and the way of life. In our research we looked at the relationship between the frequency and the ways of using social media and the styles of self-identity development by young adults. For this purpose, a group students aged 20-25 were examined using two methods: the Gurba & Gurba Questionnaire and Identity Style Inventory (ISI) [4]. Interestingly, there are no significant correlations between self-identity styles and social media and games use, but we observe positive correlation between the level of Commitment and the frequency of searching online for knowledge related to education and development.
Plasminogen Activation in Focal Cerebral Ischemia and Reperfusion

In focal cerebral ischemia the plasminogen-plasmin system plays a role in the fibrinolysis of vessel-occluding clots and also in the proteolysis of extracellular matrix components, which potentially contributes to brain edema and bleeding complications. The authors investigated the plasminogen activation after middle cerebral artery occlusion with and without reperfusion (reperfusion intervals 9 and 24 hours) in rats by histologic zymography and compared areas of increased plasminogen activation to areas of structural injury, which were detected immunohistochemically. After 3 hours of ischemia, increased plasminogen activation was observed in the ischemic hemisphere. The affected area measured 5.2% ± 8.5% and 19.4% ± 30.1% of the total basal ganglia and cortex area, respectively. Reperfusion for 9 hours after 3 hours of ischemia led to a significant expansion of plasminogen activation in the basal ganglia (68.8% ± 42.2%, P < 0.05) but not in the cortex (43.0% ± 34.6%, P = 0.394). In the basal ganglia, areas of increased plasminogen activation were related to areas of structural injury (r = 0.873, P < 0.001). No such correlation was found in the cortex (r = 0.299, P = 0.228). In this study, increased plasminogen activation was demonstrated early in focal cerebral ischemia. This activation may promote early secondary edema formation and also secondary hemorrhage after ischemic stroke.
Cytoskeletal changes induced by GRAF, the GTPase regulator associated with focal adhesion kinase, are mediated by Rho.

Graf, the GTPase regulator associated with focal adhesion kinase was previously shown to have GAP activity for &Rgr; A and Cdc42 in vitro (Hildebrand et al 1996 Mol. Cell Biol. 16: 3169-3178). In this study we sought to determine whether Graf acted at the level of Cdc42, Rho, or both in vivo and whether Graf was a signal terminator or transducer for these proteins. Microinjection of Graf cDNA into subconfluent Swiss 3T3 cells (in the presence of serum) has marked effects on cell shape and actin localization. Graf expression causes clearing of stress fibers followed by formation of long actin based filopodial-like extensions. Similar phenotypes were observed following injection of the Rho-inhibitor, C3 into these cells. The Graf response was dependent on GAP activity, since injection of Graf cDNA containing point mutations in the GAP domain (R236Q or N351V) which block enzymatic activity, does not confer this phenotype. Injection of Graf into Swiss 3T3 cells in which Rho has been down-regulated by serum starvation has no effect on cell morphology. Using this system, we demonstrate that Graf blocks sphingosine-1-phosphate (SPP) stimulated (Rho-mediated) stress fiber formation. Conversely, Graf expression does not inhibit bradykinin stimulated (Cdc42-mediated) filopodial extensions. These data indicate that Graf is a GAP for Rho in vivo. To further substantiate these results we examined the effect of Graf over-expression on Rho-mediated neurite retraction in nerve growth factor (NGF)-differentiated PC12 cells. In PC12 cells, which express relatively high levels of endogenous Graf, overexpression of Graf (but not Graf containing the R236Q mutation) enhances SPP-induced neurite retraction. These data indicate the possibility that Graf may be an effector for Rho in certain cell types.
Acoustic Characteristics of Greek Vowels

Abstract Five male speakers produced the vowels of Greek at slow and fast tempo, in lexically stressed and unstressed syllables, and in lexically stressed syllables of words appearing in focus position. Duration, fundamental frequency (F₀), amplitude, and the frequencies of the first (F1) and second formant (F2) were measured. The effects on these variables of the phonemic category of the vowel, tempo, stress, and focus were examined. The results indicated that the vowel system of Greek follows universal tendencies in terms of duration but not in terms of F₀ and amplitude. Vowels in focus position, when plotted by their F1 and F2 frequencies, defined a vowel space larger than that defined by vowels in any other condition.
Differentiation in vitro of a leukemia virus-induced B-cell lymphoma into macrophages

Cells of the hemopoietic system arise by proliferation and differentiation of progenitor cells. This process begins with multipotential stem cells which can self-renew and also undergo progressive differentiation to progenitor cells committed to particular lineages, ultimately yielding mature blood cells (D. Metcalf and M. A. S. Moore, Haematopoietic Cells, 1971). Early commitment of lymphoid progenitors is generally believed to separate the lymphoid lineage from the myeloid and erythroid lineages, whose progenitors are separated late in differentiation (Metcalf and Moore, 1971). We recently developed a derivative of Moloney murine leukemia virus (M-MuLV) in which the enhancer sequences from simian virus 40 were substituted into the M-MuLV long terminal repeat. This recombinant virus (delta Mo + SV M-MuLV) induces pre-B and B lymphoid leukemia with long latency after inoculation of 2-day-old NIH Swiss mice (R. Hanecak, P. K. Pattengale, and H. Fan, J. Virol. 62:2427-2436, 1988). In this report, we describe the derivation of a permanent, virus-producing cell line with the phenotypic characteristics of mature macrophages from a B-cell-derived lymphoblastic lymphoma induced by delta Mo + SV M-MuLV. Comparison studies of immunoglobulin heavy-chain gene rearrangements and also delta Mo + SV M-MuLV proviral integration sites confirmed that the macrophage cell line was derived from the original B-lymphoblastic lymphoma. Moreover, inoculation of the macrophage cell line into animals resulted in histiocytic sarcomas of the macrophage type, thus reflecting stable conversion of B-lymphoid tumor cells to the macrophage phenotype. These results suggest a closer relationship between lymphoid and myeloid cells than previously believed.