Miracle-dz/UniFAR-FTUs huggingface dataset:
Crystal structure of Mdm12 reveals the architecture and dynamic organization of the ERMES complex

The endoplasmic reticulum–mitochondria encounter structure (ERMES) is a protein complex that plays a tethering role in physically connecting ER and mitochondria membranes. The ERMES complex is composed of Mdm12, Mmm1, and Mdm34, which have a SMP domain in common, and Mdm10. Here, we report the crystal structure of S. cerevisiae Mdm12. The Mdm12 forms a dimeric SMP structure through domain swapping of the β1‐strand comprising residues 1–7. Biochemical experiments reveal a phospholipid‐binding site located along a hydrophobic channel of the Mdm12 structure and that Mdm12 might have a binding preference for glycerophospholipids harboring a positively charged head group. Strikingly, both full‐length Mdm12 and Mdm12 truncated to exclude the disordered region (residues 74–114) display the same organization in the asymmetric unit, although they crystallize as a tetramer and hexamer, respectively. Taken together, these studies provide a novel understanding of the overall organization of SMP domains in the ERMES complex, indicating that Mdm12 interacts with Mdm34 through head‐to‐head contact, and with Mmm1 through tail‐to‐tail contact of SMP domains.
P Wave Signal‐Averaged Electrocardiography to Identify Risk for Atrial Fibrillation

DARBAR, D. , et al.: P Wave Signal‐Averaged Electrocardiography to Identify Risk for Atrial Fibrillation. AF is the most common sustained cardiac arrhythmia, and this prevalence is increasing. The impact of AF on morbidity and mortality is substantial, as are the socioeconomic consequences like higher health care costs, chronic disease management, and disabilities. Early recognition of patients at high risk for AF, combined with effective management, may help prevent AF from becoming chronic, helping to minimize potential health risks, costs, and other complications. P wave signal‐averaged electrocardiography (SAECG) has been shown to have a potential role in identifying patients at risk of developing paroxysmal AF and those likely to change from paroxysmal AF to chronic AF. The theoretical rationale of P wave SAECG in patients with AF is delay in the intraatrial and interatrial conduction. Intraatrial conduction delays can be seen on the surface electrocardiogram as P wave prolongation, which is more visible with averaging techniques and high resolution recording devices. Averaging followed by amplification after proper filtering of the electrical signal allows more precise measurements of duration and amplitude of the P wave. Data on reproducibility, filter settings, number of beats to be averaged, and definitions of the onset and offset depend on the system used, which can be QRS or, preferably, P wave triggered. A prolonged P wave duration is one of the best predictors of perioperative AF, but the role of P wave SAECG in the paroxysmal form is less well defined. Combining P wave duration with other predictors for AF improves the diagnostic value of P wave SAECG.
Skip-free Markov decision processes

We introduce a class of models for multidimensional control problems which we call skip-free Markov decision processes, and describe and analyse an algorithm applicable to Markov decision processes that are skip-free in the negative direction. Starting with the finite average cost case, we show that the algorithm combines the advantages of both value iteration and policy iteration -- it is guaranteed to converge to an optimal policy and optimal value function after a finite number of iterations but the computational effort required for each iteration step is comparable with that for value iteration. We show that the algorithm can be easily extended to solve continuous time models, discounted cost models and communicating models, and provides new insights into the formulation of the constraints in the linear programming treatment of skip-free models.
Biocompatibility of Clearfil Liner Bond 2 and Clearfil AP-X system on nonexposed and exposed primate teeth.

OBJECTIVE Recent studies have demonstrated that acid etching of vital dentin and pulpal tissue does not retard pulpal healing, odontoblastoid cell differentiation, or dentinal bridge formation when the pulp is capped with adhesive resins. The purpose of this study was to evaluate the pulpal response in nonexposed and exposed monkey pulps to treatment with the Clearfil Liner Bond 2 and Clearfil AP-X system. METHOD AND MATERIALS Class V and Class I cavities in nonexposed and exposed pulps were observed at 7 or 8, 27, and 97 days. RESULTS There were no differences in pulpal inflammation between the Clearfil Liner Bond 2/Clearfil AP-X specimens and calcium hydroxide controls in either Class V or Class I cavities at the various time periods. CONCLUSION Clearfil Liner Bond 2 and Clearfil AP-X system is not toxic to either nonexposed or exposed pulpal tissues when placed according to manufacturer's directions.
Do Parents Matter? Effects of Lender Affiliation through the Mortgage Boom and Bust

It is widely acknowledged that the 2007 mortgage crisis was preceded by a broad deterioration in underwriting diligence. This paper shows that this deterioration varied by the industry affiliation of mortgage lenders. Loans issued by homebuilders and stand-alone lenders were significantly less likely to default than loans issued by depository banks and affiliates of major financial institutions. I argue that homebuilders and stand-alone lenders had the least financial capacity to hold mortgages, and their resulting need to sell loans quickly on the secondary market forced them to issue safer loans. Tests of other explanations, including differences in information and incentives to avoid foreclosure externalities, receive little support. This study highlights a novel means by which firm boundaries influence firm adaptation to changing market conditions by defining the boundaries of the internal capital markets and hence the relative constraints of constituent units. This paper was accepted by Bruno Cassiman, business strategy.
Un ou deux phonèmes

Abstract Les Grundzuge der Phonologie du regrette N. S. Troubetzkoy representent sans contredit le couronnement d'une decade d'activite consacree a l'elaboration progressive d'une phonetique fonctionelle et structurale. C'est l'aboutissement d'un effort collectif pour eliminer partout l'affirmation subjective et la remplacer par le critere objectif.
Autoradiographic study of histogenesis in the mouse olfactory bulb. II. Cell proliferation and migration

Cell proliferation and migration in the developing mouse olfactory bulb was studied by autoradiography. Animals were injected with thymidine‐H3 at various developmental stages and killed one to 96 hours later. All neurons arise in the germinal zone surrounding the ventricle. Until the fourteenth day of gestation (E14) this zone consists only of a matrix (primitive ependymal) layer. From E14 to E17 both matrix and subependymal layers are found, and from E18 to maturity only the subependymal layer is present. The matrix layer produces the mitral cells and some tufted and granule cells; the subependymal layer gives origin to some tufted cells and most of the granule cells. Mitral cell neuroblasts migrate peripherally to reach the primitive mitral cell layer three days after final DNA synthesis. Tufted cell neuroblasts migrate through the developing mitral cell layer to reach their definitive locations; external granule cell neuroblasts migrate past both developing mitral and tufted cells. Neuroglia arise from scattered proliferating glioblasts, originally derived from the periventricular germinal zone. Time of origin and rate of migration of olfactory bulb neurons was checked against the histological development of the bulb. A good agreement corroborated the autoradiographic method used in this study and in previous studies on time of origin of neurons in the central nervous system.
Reasons for delays in diagnosis of anal cancer and the effect on patient satisfaction.

OBJECTIVE To quantify the time to diagnosis of anal cancer after onset of symptoms, to identify reasons for delays in diagnosis, and to identify the effect of delays on patient satisfaction. DESIGN Retrospective questionnaire. SETTING Cross Cancer Institute in Edmonton, Alta. PARTICIPANTS Patients newly diagnosed with anal cancer on their first visit to the centre. MAIN OUTCOME MEASURES Timeline from first symptoms to first access to medical care and to diagnosis, and patient satisfaction. RESULTS Twenty-six patients completed the survey. Although most sought medical attention promptly, 19% waited for more than 6 months. At first visits after symptom onset, a rectal examination was performed in only 54% of patients, a diagnosis of hemorrhoids was given in 27% of patients, and further investigations were ordered in only 54% of patients. If a misdiagnosis of hemorrhoids was made, substantially more visits were required to diagnose the cancer. An average of 3.2 months after the first visit to a physician and 7.4 months after onset of symptoms was needed to obtain a diagnosis. Overall, 28% of patients believed there were no diagnostic delays and 40% of patients thought they were responsible for the delay. Overall, 72% of patients were satisfied with the care they received. Patients who were dissatisfied perceived the delay in diagnosis to be because no action was taken by a physician or the wait was too long for tests or referrals. CONCLUSION To reduce delays in diagnosis, it might be important to educate relevant populations about symptoms of anal cancer. In addition, primary care physicians must maintain a high index of suspicion of anal cancer in high-risk populations. Finally, there must be a system-wide increase in access to further investigations through gastroenterologists and general surgeons.
The effect of varying stimulus intensity on NMDA-receptor activity in cat visual cortex.

1. A study was made of the relative contribution of N-methyl-D-aspartate (NMDA) and non-NMDA receptors to the visual responses of cells in different layers of the cat visual cortex at different levels of excitatory drive (which was varied by altering the stimulus contrast). 2. Receptive fields were mapped for 121 cells in area 17 of cat cortex. Cells were characterized to determine the optimal visual stimulus, the brightness of which was then varied relative to background luminance to construct a contrast-response (C-R) curve for each cell. Curves were made during control conditions and during application of agonists (NMDA and quisqualate) and/or antagonists [(D)-2-amino-5-phosphonovaleric acid (D-APV) and 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX)] to examine the excitatory amino acid components of the visual response. 3. Threshold responses were obtained with stimuli between 1/60 and 1.8 X background luminance. The cell response, measured by firing rate, was linearly related to stimulus contrast over 1-2 decades and saturated at higher contrasts. 4. Application of APV reduced the slope of the linear portion of the C-R curve for cells located in layers II and III (average reduction, 59% of control). APV did not decrease the threshold to stimulation. The "just suprathreshold" responses to stimulation were reduced by the same proportion as the saturation responses for individual cells. The principal effect was therefore to reduce the gain of the C-R curve in these layers. 5. Application of APV reduced the spontaneous activity of cells located in layers IV, V, and VI with little if any effect on the gain of the C-R curve. This suggests a tonic background level of NMDA-receptor activation in these layers, which is not directly related to the visual response. 6. Low levels of NMDA increased the gain of the C-R curve in layers II/III and V/VI. On the other hand, low levels of quisqualate increased the overall level of firing without affecting the gain of the C-R curve. NMDA did not increase the gain of the curve in layer IV. 7. These experiments show that visual stimuli that produce just suprathreshold responses activate NMDA receptors. The degree of activation is proportionally the same for small responses and large responses for an individual cell. Rather than finding a threshold for NMDA-receptor activation, a continuous range of NMDA-receptor influence was observed over the entire response range. (ABSTRACT TRUNCATED AT 250 WORDS)
Internal ribosome entry sites in eukaryotic mRNA molecules.

Initiation of translation of most eukaryotic mRNAs commences with 5 end–dependent recruitment of 40S ribosomal subunits to the mRNA. The 40S subunit carrying the initiator methionine-tRNA and certain eukaryotic initiation factors (eIFs) is thought to scan the mRNA in a 5 to 3 direction until an appropriate start codon is encountered at which stage a 60S subunit joins to form an 80S ribosome that can decode the RNA into protein (Kozak 1989; Hershey and Merrick 2000). A subset of mRNAs contains internal ribosomal entry sites (IRESs), usually in the 5 NTR, that enable end-independent initiation to occur. IRES-containing mRNAs are not subjected to many of the regulatory mechanisms that control recruitment of most mRNAs to the translation apparatus. In this review, we briefly provide an introduction to the known mechanisms of translation initiation. Then, we discuss in detail the molecular mechanisms of IRES-mediated initiation and how they are used by specific mRNAs to permit translation under physiological circumstances such as mitosis, apoptosis, hypoxia, and some viral infections when translation of most mRNAs is repressed.
Attention-Deficit Hyperactivity Disorder (ADHD) Comorbidity: A Case for ``Pure'' Tourette Syndrome?

More than a decade of research regarding the motoric characteristics of the attention-deficit hyperactivity disorder (ADHD) that accompanies Tourette syndrome has revealed unique anatomic and neurobehavioral differences and highlighted the importance of distinguishing children with this form from the 40% of children with Tourette syndrome who do not have ADHD. This distinction is important in providing guidance to parents and to patients and in formulating expectations for short- and long-term prognoses. In addition, study methodologies that fail to categorize patients in this way and instead involve covarying for dimensional symptoms of ADHD obscure biologically distinctive circuits and clinically meaningful patient characteristics. (J Child Neurol 2006;21:701—703; DOI 10.2310/7010.2006.00164).
Physical modelling of electroporation in close cell-to-cell proximity environments

Many applications of electroporation, especially those utilizing electrofusion and in-vivo electroporation, involve cell environments that include close cell-to-cell proximity and a wide range of target cell size. It is important to understand how this kind of environment may alter optimum electroporation electrical parameters for any given application. A physical, electrically equivalent model of biological cell electroporation, based on aqueous solution filled thin latex rubber membrane spheroids, was used to investigate membrane permeabilization behaviour where there is both close cell-to-cell proximity and different cell radii. Cell model arrangements were pulsed using either a 50 µs or 10 µs, 1/e decay time constant dc capacitive discharge electric field, with peak amplitudes of 160–500 kV m−1. Results indicate that, compared to cells in isolation, electroporation initiates at substantially decreased applied electric field magnitudes in regions of close cell-to-cell proximity where the external media conductivity is lower than the cell interior conductivity, and the membrane is maximally polarized. Additionally, the use of shorter time constant, higher peak magnitude pulse parameters should reduce the relative difference in threshold membrane permeabilization in regions of close cell-to-cell proximity for cells of different size so that the degree of electroporation is more uniform for variable size and shape target cell populations.
Expression of Vascular Endothelial Growth Factor (VEGF) and its Receptors (Flt-1 and Flk-1) following Permanent and Transient Occlusion of the Middle Cerebral Artery in the Rat

Vascular endothelial growth factor (VEGH) is a known endothelial mitogen and a potent enhancer of vascular permeability although its role in focal cerebral ischemia is still not completely understood. The present report describes the immunohistochemical distribution of VEGF and its 2 receptors, Flt-1 and Flk-1 at day 1 and 3 following permanent and transient middle cerebral artery occlusion (MCAO) in the rat. A bilateral increase in VEGF immunoreactivity, Particularly in neurons and blood vessels, was seen in both the experimental designs by day 1. By day 3, the immunoreactivity was restricted chiefly to the lesion side, where reaction was most prominent in the border zones of the infarcts. Immunoreaction to VEGF was more pronounced in cases of permanent MCAO than in transient MCAO.Flt-1 reaction was increased in neurons, gilal and endothelial cells after both transient and permanent MCAO. Immunoreactivity to Flk-1 was prominent in glial cells and was present to some extent in endothelial cells. These findings indicate an early upregulation of VEGF and its receptors after permanent as well as transient focal cerebral ischemia in the rat.
The factor structure of the GHQ: a scaled version for a hopital's general practice service in Mexico

SYNOPSIS This paper reports the factor structure of the symptoms comprising the GHQ when it is administered in the general practiāe service of a hospital. Two shorter versions are proposed: one with 6 scales and 30 items, and the other with 4 scales and 28 items. The latter is compared with the 28-item English version. Preliminary data concerning the validity of the scales are presented. In a comparison of the screening potentiality of the 60- and 28-item versions, no significant differences were found.
Identification of Binding Sites for Neutralizing Monoclonal Antibodies on the 14-kDa Fusion Protein of Orthopox Viruses

A 14-kDa gene-specific probe of vaccinia virus Western Reserve (WR) hybridized to homologous sequences in the genomes of the orthopox virus species cowpox, camelpox, mousepox, and monkeypox virus. The corresponding genes were mapped and sequenced. Homologies of more than 95% were found when compared to the 14-kDa gene of vaccinia virus WR. However, point mutations which led to alterations in the amino acid sequences were mainly located between residues 26 and 40. By use of synthetic peptides, this part of the 14-kDa fusion protein could be identified as the binding site for four different neutralizing monoclonal antibodies.
Temporal regulation of the Bacillus subtilis early sporulation gene spo0F

The initiation of sporulation in Bacillus subtilis depends on seven genes of the spo0 class. One of these, spo0F, codes for a protein of 14,000 daltons. We studied the regulation of spo0F by using spo0F-lacZ translational fusions and also measured Spo0F protein levels by immunoassays. spo0F-lacZ and Spo0F levels increased as the cells entered the stationary phase, and this effect was repressed by glucose and glutamine. Decoyinine, which lowers GTP levels and allows sporulation in the presence of normally repressing levels of glucose, induced spo0F-lacZ expression and raised Spo0F levels. The expression of spo0F-lacZ was dependent on spo0A, -0B, -0E, -0F, and -0H genes, a spo0H deletion causing the strongest effect. In most respects, the spo0F gene was regulated in a manner similar to that of spoVG. However, the presence of an abrB mutation did not relieve the dependence of spo0F gene expression on spo0A, as it does with spoVG (P. Zuber and R. Losick, J. Bacteriol. 169:2223-2230, 1987).
Socioeconomic, Demographic, and Geographic Variables Affecting the Diverse Degrees of Consanguineous Marriages in Spain

In a population the inbreeding coefficient ;ga is determined by the relative incidence of the various degrees of consanguineous marriages—uncle-niece or aunt-nephew (C12), first cousin (C22), first cousin once removed (C23), second cousin (C33)—which may be related to temporal, geographic, demographic, and economic factors. Using published information from Spain corresponding to urban and rural areas, in this article we seek to establish how each specific relationship behaves with respect to geographic, demographic, and socioeconomic factors, to determine differential urban-rural patterns, and to study whether the diverse types of consanguineous matings relate homogeneously to these factors. For this purpose we performed multiple regressions in which the dependent variables were the different degrees of consanguinity previously selected and the independent variables were geographic, demographic, and economic factors. Our results indicate that the various types of consanguineous marriages in Spain are more conditioned by geographic, demographic, and economic variables than by the inbreeding level ;ga (the coefficient of determination was between 0.22 and 0.72; the maximum for ;ga was 0.35). A regional pattern exists in Spain and corresponds to close and to remote kinship, which may be mainly related to economic and family factors. Close relationships appear to be more associated with economic variables, whereas second-cousin marriages correspond largely to rural areas of the Spanish Central Plateau.
Epitope location of 13 anti-gag HIV‐1 monoclonal antibodies using oligopeptides and their cross reactivity with HIV‐2

A series of 15-mer oligopeptides which overlapped by five amino acids (AA) across the p24 of HIV-1SF2 and a similar series across the p18 of HIV-1SF2 were used to identify the locations of 13 anti-gag monoclonal antibodies (MAbs). Three anti-p24 MAbs recognized sequences within the first 50 AA of the amino-terminal. Another anti-p24 recognized a conformational epitope in the centre of the protein and this MAb cross-reacted with two HIV-2 isolates suggesting conservation of this epitope between HIV-1 and HIV-2. One anti-p24 MAb recognized a linear sequence in the carboxy-terminal 100 AA and one p24 antibody was assumed to recognize a truly conformational epitope as it did not react with any of the linear peptides. Four anti-p18 MAbs were located at the carboxy-terminus of p18 with another MAb mapping slightly inwards from the carboxy-terminus and one anti-p18 MAb failed to bind to the p18 peptides. The carboxy-terminal distribution of the p18 MAbs indicated a highly immunogenic nature for this region in mice. None of the anti-p18 MAbs showed cross-reactivity with HIV-2 isolates, confirming the greater sequence variability of p18 over p24.
The Theory of Planned Behavior: Predicting Teachers’ Intentions and Behavior during Fitness Testing

The twofold purpose of this study was to develop and validate an instrument that assessed teachers’ intentions, attitudes, subjective norm, and perceived behavior control to administer fitness tests effectively, and to determine how well the instrument could predict teachers’ intentions and actual behavior based on Ajzen’s (1985, 1991) theory of planned behavior. In the development phase of the study, 104 physical educators completed the pilot version of the survey to refine the instrument. In the prediction of behavior phase of the study, a convenience sample of 195 physical educators completed (a) the Teachers’ Intentions to Administer Physical Fitness Tests Effectively (TIAPFTE) before fitness testing and (b) a behavior self-report after they administered fitness testing. Standard multiple regression analyses showed perceived behavioral control and attitude significantly predicted intention. Furthermore, results showed that attitude significantly predicted teachers’ behavior directly.
Microbial Transformation of Danazol

Danazol (17 -hydroxy-17 -pregna-2,4-dien-20-yno-[2,3- d ] isoxazole) ( 1 ) on fermentation with Fusarium lini , Aspergillus niger , and Cephalosporium aphidicola yielded 17 -hydroxy-2-(hydroxymethyl)-17- -pregn-4-en-20-yn-3-one ( 2 ) and 17 -hydroxy-2-(hydroxymethyl)-17 -pregna-1,4-dien-20-yn-3-one ( 3 ), while the fermentation of 1 with Bacillus cerus yielded compound 2 only.