Miracle-dz/UniFAR-FTUs huggingface dataset:
Robust Search Methods for Rational Drug Design Applications

The main topic of this thesis is the development of computational search methods that are useful in drug design applications. The emphasis is on exhaustiveness of the search method such that it can guarantee a certain level of geometric accuracy. In particular, the following two problems are addressed: (i) Prediction of binding mode of a drug molecule to a receptor and (ii) prediction of crystal structures of drug molecules. Predicting the binding mode(s) of a drug molecule to a target receptor is pivotal in structure-based rational drug design. In contrast to most approaches to solve this problem, the idea in this work is to analyze the search problem from a computational perspective. By building on top of an existing docking tool, new methods are proposed and relevant computational results are proven. These methods and results are applicable for other place-and-join frameworks as well. A fast approximation scheme for the docking of rigid fragments is described that guarantees certain geometric approximation factors. It is also demonstrated that this can be translated into an energy approximation for simple scoring functions. A polynomial time algorithm is developed for the matching phase of the docked rigid fragments. It is demonstrated that the generic matching problem is NP-hard. At the same time the optimality of the proposed algorithm is proven under certain scoring function conditions. The matching results are also applicable for some of the fragment-based de novo design methods. On the practical side, the proposed method is tested on 829 complexes from the PDB. The results show that the closest predicted pose to the native structure has the average RMS deviation of 1.06 Å. The prediction of crystal structures of small organic molecules has significantly improved over the last two decades. Most of the new developments, since the first blind test held in 1999, have occurred in the lattice energy estimation subproblem. In this work, a new efficient systematic search method that avoids random moves is proposed. It systematically searches through the space of possible crystal structures and conducts search space cuts based on statistics collected from the structural databases. It is demonstrated that the fast search method for rigid molecules can be extended to include flexible molecules as well. Also, the results of some prediction experiments are provided showing that in
A Computer-Controlled Travelling Flux Detector System for CANDU Reactors

A transportable Travelling Flux Detector system for use on CANDU power reactors has been developed and tested at the Chalk River Nuclear Laboratories. This system consists of a mniniature fission clhamber on a motorized winch housed in a lead shielding flask. The movement of the fission chamber and the collection of data are handled by a microcomputer located near the flask on the reactor deck, while data storage and later analysis are handled by another microcomputer at a remote location.
Natural History of Nonoperatively Treated Symptomatic Rotator Cuff Tears in Patients 60 Years Old or Younger

Background: Rotator cuff tears are the most frequent tendon injury in the adult population. However, the natural history of nonoperatively treated full-thickness tears is poorly defined. Knowledge of the expected evolution in tear size is important when considering nonoperative versus surgical care, especially in relatively young, active patients. Purpose: To evaluate the size change of nonoperatively treated full-thickness rotator cuff tears over 2 to 3 years’ follow-up. Study Design: Case series; Level of evidence, 4. Methods: The authors prospectively followed patients 60 years old or younger who had a full-thickness rotator cuff tear equal to or larger than 5 mm, as diagnosed by bilateral shoulder ultrasound, and who were treated nonoperatively. At 2 to 3 years after the index ultrasound examination, a repeat ultrasound examination was performed by the same ultrasonographer. Results of the follow-up ultrasound examinations of both shoulders were compared with those of the index ultrasound examinations for change in rotator cuff tear size. The correlations were examined between these changes and age, sex, history of initial trauma, size of tear on the index ultrasound, and current shoulder symptoms. Results: Fifty-one patients with 61 rotator cuff tears were evaluated. At a follow-up of 25 to 39 months (mean, 29), 49% of the tears (30 tears) increased in size, 43% (26 tears) had not changed, and 8% (5 tears) decreased in size. For 25% (10 shoulders ) of initially intact shoulders (41 shoulders), a new full-thickness rotator cuff tear was diagnosed. No correlation was found between the change in tear size and age of the patient (P = .85), sex (P = .93), existence of a prior trauma (P = .63), size of tear at index ultrasound (P = .62), and bilateral tears (P = 1.00). There was a correlation between the existence of considerable pain at the time of the follow-up ultrasound and a clinically significant increase in tear size (P = .002). Conclusion: Full-thickness rotator cuff tears tend to increase in size in about half of patients aged 60 years or younger. Surgery should be initially considered in these patients to prevent a probable increase in size tear. Patients treated nonoperatively should be routinely monitored for tear size increase, especially if they remain symptomatic.
Molecular diversity at the CYP2D6 locus in healthy and schizophrenic southern Brazilians.

AIMS The delineation of allele distribution and frequency is required to effectively translate pharmacogenetics to the clinic and given the paucity of CYP2D6 data in the Brazilian population, the purpose of this research was to characterize CYP2D6 alleles and genotype frequencies in Brazilians of European and African ancestries. Moreover, since it is suggested in the literature that CYP2D6 poor metabolism might be involved with susceptibility to schizophrenia, we included data from Brazilian schizophrenic patients to verify if CYP2D6 poor metabolism phenotypes are associated with susceptibility to schizophrenia. MATERIALS & METHODS We investigated 24 CYP2D6 polymorphisms, gene deletions and gene multiplications in 179 healthy individuals from Brazil, 92 of European descent and 87 African Brazilians. CYP2D6 gene polymorphisms were genotyped by a MassARRAY SNP genotyping system. RESULTS A total of 19 different alleles and five allele duplications were identified in African and European Brazilians. No significant differences in CYP2D6 allele function or poor metabolizer predicted phenotype frequencies were observed between healthy controls and schizophrenic patients, but the predicted metabolic phenotype distribution showed a significant higher frequency of intermediate metabolizers in African Brazilians than in European Brazilians (p = 0.001). CONCLUSIONS CYP2D6 poor metabolizer genotype seems not to be a determining factor of schizophrenia susceptibility in Brazilians. The characterization of CYP2D6 variability will be very useful for future pharmacogenetic studies in the Brazilian population.
Sparse MEG Source Imaging For Reconstructing Dynamic Sources of Interictal Spikes in Partial Epilepsy

Purpose: The present study aimed to test the feasibility of a novel neuroimaging technique, that is, variation-based sparse cortical current density (VB-SCCD) imaging algorithm, in noninvasively estimating location and extent of epileptic sources from interictal magnetoencephalography (MEG) data. Methods: A total of 108 interictal spikes from 3 partial epilepsy patients were selected to perform VB-SCCD source analysis. Cortical sources were identified at spike peaks, rising phases, and entire spikes, respectively, from all interictal spikes in each patient, to estimate source locations and extents, and validated using presurgical evaluation data. Other source analysis methods, that is, minimum norm estimate and sparse source imaging were also performed for comparison. Results: Cortical sources reconstructed by VB-SCCD that are consistent with clinical presurgical evaluation outcomes have detection rates of 65.8% at spike peaks, 85.1% during rising phases, and 92.6% in entire spikes. Stable spatiotemporal patterns of reconstructed cortical sources were also obtained using VB-SCCD, which provide more insights about the formation and propagation of interictal epileptic activity. Conclusions: Our present results suggest that the VB-SCCD technique has the capability in estimating location and extent of epileptic sources of interictal spikes and is promising to become a valuable noninvasive tool in assisting presurgical planning for partial epilepsy patients.
MORPHOMETRIC STUDY OF STERNUM FOR DETERMINATION OF SEX *

Determination of sex from human skeletal remains for forensic and medico-legal purpose is an integral part. Study of the sternum as an individual parameter for determination of sex has been attempted by various workers. The material for the present study consists of 50 (27 Male, 23 Female) sterna obtained from the cadavers. The sterna were removed from the cadavers by sectioning the costal cartilages just besides the costochondral junction. Cases belonging to age more than 15 years were only considered. The lengths of the manubrium in the male sterna vary from 35 mm to 71 mm. The Mean was calculated and found to be 52 mm. The Standard Deviation (S.D.) for the length of the manubrium for males is ± 8. The lengths of manubrium in the female sterna vary in the range of 41 mm to 61 mm. The Mean is 48 mm and the S.D. is ± 5. The lengths of the body in male sterna were in the range of 59 133 mm. The Mean is 98 mm and S.D. ± 18. The lengths of the body in female sterna were in the range of 56 96 mm. The combined lengths (M+B) in the male cases are in the range from 1 0 1 1 9 1 mm. The combined lengths in the female cases are in the range from 98 -150mm. the sternal indices for males are in range of 38 – 77 mm. while the female cases are in the range 46 – 78 mm. The widths of the manubria of male sterna were in the range of 38 – 72 mm. The widths of the Manubria of female sterna were in the range of 42-68 mm with Mean 54 mm. The widths of the body of the sterna in males were in the range 2 1 6 2 m m . The widths of the body of the sterna in females were in the range 2 4 5 1 m m .
Topical Khellin and Natural Sunlight in the Outpatient Treatment of Recalcitrant Palmoplantar Pompholyx: Report of an Open Pilot Study

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Manipulation of Host Vesicular Trafficking and Membrane Fusion During Chlamydia Infection

Chlamydia infections are associated with a wide range of diseases. C. trachomatis (serovars A, B, Ba and C) causes trachoma, the world’s leading cause of infectious blindness. Serovars D through K are most commonly associated with sexually transmitted diseases and can cause infertility in women if left untreated [Paavonen and Eggert-Kruse, 1999]. Sexually transmitted diseases (STDs) are prevalent in every society in the world, including in developed countries (United States Centers for Disease Control [CDC]). Therefore, they represent a serious public health concern. Public programs aimed at increasing people’s awareness of the risks these pathogens pose have helped in controlling the spread of disease. Nevertheless, Chlamydia is still the most frequently reported STD in the United States. In 2009, 1.2 million new cases of Chlamydia infections were reported in the United States alone, but the actual number of infections is estimated to be higher due to a large number of unreported cases (CDC). Vaccination is the gold standard for disease prevention, but despite years of research, no vaccines exist for bacterial STDs. The typical course of treatment for Chlamydia infections involves the use of antibiotics, but there is emerging evidence that non-specific antibacterial agents can cause lasting damage to an individual by adversely affecting the homeostasis of the microbiota, which is the collection of bacteria that positively affect normal human functioning [Stewardson et al., 2011].
AIS Electronic Library (AISeL)

This paper (work in progress) investigates how the individual’s concern for information privacy affects the adoption of biometric technologies. Biometrics refers to the automated authentication of an individual based on his/her distinguishing characteristics (Bolle et al. 2004). Given the very personal nature of biometric technologies, their adoption may be inhibited by individual’s concern for information privacy. This research develops a model of biometrics adoption that integrates information privacy and TAM. This model aims to assist researchers and practitioners in understanding the factors that affect biometrics adoption. To examine the effects of TAM and privacy on intentions to use biometric technology, a pretested instrument will be administered to medical personnel who use finger scanning equipment to retrieve drugs in a hospital.
High-normal blood pressure, functional capacity and left heart mechanics: Is there any connection?

Abstract Objective. To evaluate the relationship between functional capacity and left ventricular (LV) and left atrial (LA) myocardial deformation, assessed by two- and three-dimensional (2DE and 3DE) strain analysis, in subjects with high-normal blood pressure (BP). Methods. This cross-sectional study included 64 subjects with optimal BP and 75 subjects with high-normal BP of similar gender and age. All the subjects underwent a complete 2DE and 3DE examination and cardiopulmonary exercise testing. Results. 3DE global longitudinal strain was significantly lower in the group with high-normal BP than in the optimal BP group (− 20.1 ± 2.4 vs − 18.5 ± 2.3%, p < 0.001). Similar results were obtained for 3DE global circumferential strain (− 21.8 ± 2.6 vs − 19.3 ± 2.4%, p < 0.001), as well as for 3DE global radial strain (45.1 ± 8.8 vs 42.3 ± 7.2%, p = 0.042), and 3DE global area strain (− 30.1 ± 4.2 vs − 28.1 ± 3.8%, p < 0.001). LV twist was similar between the observed groups, whereas untwisting rate was significantly decreased in the subjects with high-normal BP (− 123 ± 30 vs − 112 ± 26°/s, p = 0.023). Peak VO2 was significantly lower in the high-normal BP group (30.8 ± 4 vs 28.3 ± 3.7 ml/kg/min, p < 0.001). 2DE LV ejection fraction (β = 0.38, p = 0.014), 2DE global longitudinal strain (β = 0.35, p = 0.019) and 3DE global longitudinal strain (β = 0.27, p = 0.042) were independently associated with peak VO2. Conclusion. LV and LA mechanics, as well as functional capacity are significantly impaired in the subjects with high-normal BP. LV and LA myocardial deformations are associated with peak oxygen uptake.
Uncertainty Reduction, Self-Enhancement, and Ingroup Identification

Two experiments tested the prediction that uncertainty reduction and self-enhancement motivations have an interactive effect on ingroup identification. In Experiment 1 (N = 64), uncertainty and group status were manipulated, and the effect on ingroup identification was measured. As predicted, low-uncertainty participants identified more strongly with a high- than low-status group, whereas high-uncertainty participants showed no preference; and low-status group members identified more strongly under high than low uncertainty, whereas high-status group members showed no preference. Experiment 2 (N = 210) replicated Experiment 1, but with a third independent variable that manipulated how prototypical participants were of their group. As predicted, the effects obtained in Experiment 1 only emerged where participants were highly prototypical. Low prototypicality depressed identification with a low-status group under high uncertainty. The implications of these results for intergroup relations and the role of prototypicality in social identity processes are discussed.
Exploring Satisfaction with and Trust in Social Networking Sites through the Lens of Fan Pages: Uncertainty Reduction and General Systems Theory Perspective

The purpose of this study is to examine social networking sites (SNS) users’ overall satisfaction with and trust in SNS, as related to their activities of visiting fan pages. We employ two theories—uncertainty reduction theory (URT) and general systems theory (GST)—to examine antecedents affecting overall satisfaction with and trust in SNS. Using a web-based survey, we analyzed 200 SNS users who follow at least one company’s fan page, and utilized seemingly unrelated regression (SUR) models to empirically test our hypotheses. Our findings indicate that uncertainty reduction strategies supported by URT are significantly associated with perceived usefulness of companies’ posts in their fan pages. In turn, perceived usefulness of those posts promotes more visits to the fan page. Finally, users’ perceived usefulness of fan page posts eventually accounts for the overall satisfaction with and trust in SNS. The implications and limitations are discussed at the end of this study.
Serum KL-6 level as an indicator of active or inactive interstitial pneumonitis associated with connective tissue diseases.

OBJECTIVE To elucidate the cut off levels of serum KL-6 indicating patients with interstitial pneumonitis (IP) and patients with active IP associated with connective tissue diseases (CTDs). METHODS CTD patients whose serum KL-6 level was measured were included. IP was diagnosed on the basis of medical records including XP/CT findings, and active IP was assumed in case that intervention for IP was newly added. The cut off levels were determined by receiver operating characteristic (ROC) curve analysis. RESULTS Among 240 (174 females) patients, 67 (42) had IP and 15 (9) had active IP. The ages of patients with and without IP, and with active IP and with inactive IP were 70.3±9.5 and 62.8±15.3, and 72.8±8.1 and 69.6±9.8, respectively. IP was significantly more prevalent in males and the elderly. The KL-6 levels were 990±90 and 301±12 U/mL in patients with and without IP, and 1,905±236 and 726±54 U/mL in those with active IP and with inactive IP, respectively. ROC curve analysis showed a cut off level of 509 U/mL for indicating IP, and that of 1,051-1,060 U/mL for indicating active IP. CONCLUSION A serum KL-6 level of higher than 500 U/mL is a marker of the presence of IP, and a level of higher than 1,000 U/mL is a marker of the presence of active IP associated with CTDs.
Activating mutations of Tn3 resolvase marking interfaces important in recombination catalysis and its regulation

Catalysis of DNA recombination by Tn3 resolvase is conditional on prior formation of a synapse, comprising 12 resolvase subunits and two recombination sites (res). Each res binds a resolvase dimer at site I, where strand exchange takes place, and additional dimers at two adjacent ‘accessory’ binding sites II and III. ‘Hyperactive’ resolvase mutants, that catalyse strand exchange at site I without accessory sites, were selected in E. coli. Some single mutants can resolve a res × site I plasmid (that is, with one res and one site I), but two or more activating mutations are necessary for efficient resolution of a site I × site I plasmid. Site I × site I resolution by hyperactive mutants can be further stimulated by mutations at the crystallographic 2–3′ interface that abolish activity of wild‐type resolvase. Activating mutations may allow regulatory mechanisms of the wild‐type system to be bypassed, by stabilizing or destabilizing interfaces within and between subunits in the synapse. The positions and characteristics of the mutations support a mechanism for strand exchange by serine recombinases in which the DNA is on the outside of a recombinase tetramer, and the tertiary/quaternary structure of the tetramer is reconfigured.