Miracle-dz/UniFAR-FTUs huggingface dataset:
HIV-1 evolution in gag and env is highly correlated but exhibits different relationships with viral load and the immune response

Objective:To evaluate relationships between HIV-1 evolution, including immune evasion, and markers of disease progression during chronic infection. Design:HIV-1 evolution and disease progression markers were evaluated over approximately 5 years of infection among 37 Kenyan women from a prospective, seroincident cohort. Evolution was measured in two genes, gag and env, which are primary targets of cellular and humoral immune responses, respectively. Methods:Proviral HIV-1 gag and env sequences were obtained from early and chronic infection when plasma viral load and CD4 cell counts were available. Human leukocyte antigen types were obtained to identify changes in gag cytotoxic T-lymphocyte epitopes. The breadth of the neutralizing antibody response was measured for each woman's plasma against a panel of six viruses. Tests of association were performed between virus evolution (diversity, divergence, and ratio of nonsynonymous to synonymous divergence), markers of disease progression (viral load and CD4 cell count), and immune parameters (gag cytotoxic T lymphocyte epitope mutation and neutralizing antibody breadth). Results:HIV-1 gag and env diversity and divergence were highly correlated in early and late infection. Divergence in gag was strongly correlated with viral load, largely because of the accumulation of synonymous changes. Mutation in gag cytotoxic T-lymphocyte epitopes was associated with higher viral load. There was evidence for adaptive evolution in env, but the extent of env evolution was only weakly associated with neutralizing antibody breadth. Conclusion:Our results indicate that HIV-1 evolution in gag and env is highly correlated but exhibits gene-specific differences. The different immune pressures on these genes may partly explain differences in evolution and consequences for HIV-1 disease progression.
Clinical Experience with Limited Lymph Node Dissection for Prostate Cancer in Korea: Single Center Comparison of 247 Open and 354 Robot-Assisted Laparoscopic Radical Prostatectomy Series

Purpose There are limited data on the role of limited pelvic lymph node dissection (PLND) in patients with prostate cancer in Korea. The objective of this study was to demonstrate our clinical experience with limited PLND and the difference in its yield between open retropubic radical prostatectomy (RRP) and robot-assisted laparoscopic radical prostatectomy (RALP) for prostate cancer patients in Korea. Materials and Methods We retrospectively analyzed 601 consecutive patients undergoing radical prostatectomy and bilateral limited PLND by either RRP (n=247) or RALP (n=354) in Asan Medical Center. All patients were divided into three groups according to the D'Amico's risk stratification method. Clinicopathologic data, including the yield of lymph nodes, were thoroughly reviewed and compared among the three risk groups or between the RRP and RALP subjects. Results The mean patient age was 64.9 years and the mean preoperative prostate-specific antigen was 9.8 ng/ml. The median number of removed lymph nodes per patient was 5 (range, 0 to 20). The numbers of patients of each risk group were 167, 199, and 238, and the numbers of patients with tumor-positive lymph nodes were 1 (0.6%), 4 (2.0%), and 17 (7.1%) in the low-, intermediate-, and high-risk groups, respectively. In the high-risk group, the lymph node-positive ratio was higher in RRP (14.9%) than in RALP subjects (2.4%). Conclusions We speculate that limited PLND may help in prostate cancer staging in intermediate- and high-risk prostate cancer groups. RRP is a more effective surgical modality for PLND than is RALP, especially in high-risk prostate cancer groups.
Students’ perception of the characteristics of effective bedside teachers

Background and methods: To determine a student perspective of the characteristics of ideal bedside teachers, a 25-item questionnaire was administered to 84 final-year medical students. The items were constructed to check for two domains of ‘Communication’ and of ‘Demographics’. The former included behaviours such as providing constructive feedback, respecting patient confidentiality and encouraging critical thinking, while the latter included characteristics such as gender, academic rank and language skills. Results: The students identified the characteristics in the ‘Communication’ domain as being far more important determinants of ideal bedside teaching than the ‘Demographics’ domain. Factor analysis showed that of the questions designed to determine communication all but one loaded unequivocally into a single factor, while the demographics were best described by two additional factors. Both these factors represented teacher properties that were difficult or impossible for the teacher to modify, while those in the communication domain were all amenable to change. Conclusions: These results are consistent with data from the literature on the broader aspects of clinical teaching, and imply that the ideal bedside teaching experience from the perspective of the students is heavily influenced by teacher behaviours than that can be modified. Practice points Students' views of the ideal bedside teaching experience fall into two broad domains. Factors concerned with “communication” are closely correlated with teaching excellence. Factors concerned with “demographics” play an inconsistent role in good teaching. The most important determinants are things that are within the instructors power to change.
Individual differences and the canalization of human behavior.

Gottlieb (1991) suggests that behavior geneticists and developmental psychologists have underestimated the importance of environmental regulation of species-typical behavior, outlines a theory of how environments and genes interact dynamically as behavior develops, and provides supporting examples from his own and others' laboratories. Although oversimplified explanations of development have occasionally gained currency, we contend that the complexities of genotype-environment relations have been addressed in psychology, with still greater difficulties arising from psychologists1 interest in individual differences in behavior. The complexities of studying genetic and environmental determination of the development of individual differences are explored, using intelligence as an example. Finally, we outline a research program in the spirit of Gottlieb's contribution. Variety is said to be the spice of life. It is a staple of necessity to geneticists. (Dobzhansky, 1967, p. 42). Man is not just an overgrown Drosophila. (Dobzhansky, 1967, p. 47)
Unipolar depression and hippocampal volume: Impact of DNA sequence variants of the glucocorticoid receptor gene

Glucocorticoid receptor (GR) plays a major role in regulation of the hypothalamic–pituitary–adrenocortical (HPA) system; HPA dysregulation represents the most consistent biological pattern of depression. Multiple functional polymorphisms are known for the GR gene, which might influence the development of unipolar depression. Previous studies reported associations to some variants in this gene but not consistently so. We investigated seven genetic polymorphisms in the GR gene (NR3C1) located in the putative promoter, exon 2 and intron 2 region. Study populations were 322 German inpatients with recurrent unipolar depression, and 298 German controls recruited from the general population. The relationships between intermediate phenotypes (hippocampal and amygdala volumes) and NR3C1 DNA sequence variants were additionally explored in a subpopulation of patients. We found association between the diagnosis of depression and DNA sequence variants in intron 2 as well as in the 5′ region of the NR3C1 gene but not for the previously studied exon 2 and putative promoter variants (global test after control of multiple testing, P = 0.02). In patients, diagnosis‐related alleles were also associated to hippocampal volume reduction and amygdala volume variation. Unipolar depression is associated with DNA variants of the NR3C1 gene in our population. Neurobiological underpinnings of depression as volumetric reductions of the hippocampus may also be mediated by variants in this gene. © 2008 Wiley‐Liss, Inc.
Biological properties of chimeric domain-deleted anticarcinoma immunoglobulins.

CC49 is a second-generation monoclonal antibody (MAb) that has high affinity for the tumor-associated pancarcinoma antigen tumor-associated glycoprotein-72. In clinical trials using gamma scanning, radiolabeled CC49 has facilitated the detection of more than 90% of carcinomas. We report here the development of a constant heavy-chain 2 (CH2) domain-deleted chimeric (c) CC49 MAb by transfecting an expression construct consisting of the CC49 murine variable region and a CH2 domain-deleted human IgG1 constant region into cCC49 kappa producing SP2/0 murine myeloma cells. As determined by SDS-PAGE, the intact cCC49 delta CH2 has a molecular weight of 153,000 and, under reducing conditions, molecular weights of 43,000 and 27,000. The plasma clearance and tumor-targeting properties of cCC49 delta CH2 were evaluated and compared with those of mouse/human chimeric forms cCC49 delta CH1 and intact cCC49. Previous studies have shown that the in vitro antigen-binding properties of cCC49 delta CH1 are similar to those of cCC49. Biodistribution studies reported here, using 131I-labeled cCC49 delta CH1 and 125I-labeled cCC49 in athymic mice bearing human colon carcinoma xenografts, demonstrated that both cMAbs localized to the tumor and cleared from the normal tissues similarly. However, in comparison with 125I-labeled cCC49, 131I-labeled cCC49 delta CH2 localized to tumors earlier and had a significantly lower percentage of the injected dose of cMAb/g (%ID/g) in normal tissues than cCC49. Immunoscintigraphy of 131I-labeled cCC49 delta CH2 and 125I-labeled cCC49 in athymic mice bearing human tumor xenografts demonstrated a clear image of the tumor by 24 h after i.v. administration of the delta CH2 cMAb versus the 72 h required for cCC49. Biodistribution studies using 177Lu-conjugated cCC49 delta CH1 and cCC49 showed no significant difference between the radiolocalization indices (% ID/g in tumor divided by % ID/g in normal tissue). 177Lu-conjugated cCC49 delta CH2, however, had lower % ID/g values in tumor xenografts and lower radiolocalization indices than either 177Lu-conjugated cCC49 delta CH1 or 177Lu-conjugated cCC49. Pharmacokinetic studies in non-tumor-bearing athymic mice using cCC49 delta CH1 and cCC49 revealed no significant difference between these cMAbs. However, the plasma clearance of cCC49 delta CH2 in non-tumor-bearing mice was significantly faster than that of cCC49. These results were similar when the cMAbs were labeled with either iodine or lutetium. In nonhuman primates, 131I-labeled cCC49 delta CH2 cleared significantly faster than 125I-labeled cCC49. The similar plasma clearance and tumor localization of cCC49 and cCC49 delta CH1 suggest that these two cMAbs may be used in similar clinical settings. However, because of the unique pharmacokinetics and tumor targeting of cCC49 delta CH2 versus cCC49 or cCC49 delta CH1, this chimeric immunoglobulin form may be useful in clinical settings that require efficient tumor targeting and rapid serum and whole-body clearance.
Dynamic equilibrium mechanism for surface nanobubble stabilization.

Recent experiments have convincingly demonstrated the existence of surface nanobubbles on submerged hydrophobic surfaces. However, classical theory dictates that small gaseous bubbles quickly dissolve because their large Laplace pressure causes a diffusive outflux of gas. Here we suggest that the bubbles are stabilized by a continuous influx of gas near the contact line, due to the gas attraction towards hydrophobic walls [Dammer and Lohse, Phys. Rev. Lett. 96, 206101 (2006); 10.1103/PhysRevLett.96. 206101Zhang, Phys. Rev. Lett.10.1103/PhysRevLett.98. 136101 98, 136101 (2007); 10.1103/PhysRevLett.98. 136101Mezger, J. Chem. Phys. 128, 244705 (2008)10.1063/1.2931574]. This influx balances the outflux and allows for a metastable equilibrium, which, however, vanishes in thermodynamic equilibrium. Our theory predicts the equilibrium radius of the surface nanobubbles, as well as the threshold for surface nanobubble formation as a function of hydrophobicity and gas concentration.
Genetic heterogeneity of the precore and the core promoter region of genotype C hepatitis B virus during lamivudine therapy

It has been reported that spontaneous or interferon (IFN)‐induced hepatitis B e (HBe) seroconversion has usually been associated with the development of a stop codon in the precore region. However, the difference between lamivudine‐induced seroconversion and spontaneous or IFN‐induced seroconversion is not known. The aim of this study was to investigate the correlation between the evolution of the precore and core promoter mutations and lamivudine‐induced seroconversion. Forty‐five patients with chronic hepatitis B virus (HBV) infection who were treated with lamivudine for more than 1 year were enrolled. The nucleotide sequence of the precore and core promoter region was determined before and after treatment with lamivudine for 1 year. Among 29 patients who were hepatitis B e antigen (HBeAg)‐positive before treatment, 12 (41.3%) lost HBeAg during the course of treatment for 1 year. Of these, eight patients (66.7%) still had precore wild type HBV after 1 year. After 1 year, reversion to precore wild type HBV was detected in 11 (64.7%) of 17 patients who had precore mutant HBV before treatment. Twelve (70.6%) of 17 patients who were persistently HBeAg‐positive had precore wild type HBV before and after treatment for 1 year. Despite the loss of HBeAg, two thirds of the patients still had precore wild type HBV after the 1‐year treatment. It is suggested that lamivudine‐induced seroconversion differs from spontaneous or IFN‐induced seroconversion in the change of nucleotides in the precore region. The reversion in the precore region may be caused by the difference of drug‐susceptibility to lamivudine. The antiviral effect of lamivudine may be more effective in the precore mutant HBV than in the precore wild type HBV. J. Med. Virol. 72:26–34, 2004. © 2004 Wiley‐Liss, Inc.
Ischemia Modified Albumin in Normal Pregnancy and Preeclampsia

Objective. Ischemia-modified albumin (IMA) has emerged as a new biomarker of myocardial ischemia. Currently, no information is available on maternal IMA levels during normal and complicated pregnancy. Preeclampsia is associated with ischemia and increased formation of free radicals in the placenta. We therefore hypothesized that production of IMA may occur in women with preeclampsia. Methods. Serum IMA and albumin concentrations were assessed in 12 patients with preeclampsia, 12 normal pregnant controls, and 12 nonpregnant controls. IMA levels were compared between groups and corrected for albumin by multivariate regression analysis. Results. Mean IMA levels were elevated in normal pregnant controls (107.3 U/mL; 95% CI, 102.5 to 112.01), compared with nonpregnant controls (94.5 U/mL; CI, 89.4 to 99.6; p = 0.015). In patients with preeclampsia, IMA levels were similar to those in normal pregnant controls (109.7 U/mL; CI, 102.2 to 117.2; p = 0.65). Also, no difference in IMA levels was observed between women with preeclampsia who delivered small-for-gestational-age (SGA) infants (99.0 U/mL; CI, 87.9 to 110.1; p = 0.13) and women with preeclampsia but without SGA. Conclusion. Serum IMA, which has been advocated as a clinical marker of cardiac ischemia, appears to be elevated during normal pregnancy. We found no significant relationship between IMA levels and preeclampsia, in women with or without SGA infants.
Femtosecond laser inscription of optical circuits in the cladding of optical fibers

Femtosecond laser inscription of optical circuits in the cladding of optical fibers Jason R. Grenier Doctor of Philosophy Graduate Department of the Edward S. Rogers Sr. Department of Electrical and Computer Engineering University of Toronto 2016 The aim of this dissertation was to address the question of whether the cladding of single-mode fibers (SMFs) could be modified to enable optical fibers to serve as a more integrated, highly functional platform for optical circuit devices that can efficiently interconnect with the pre-existing fiber core waveguide. The approach adopted in this dissertation was to employ femtosecond laser direct writing (FLDW), an inherently 3D fabrication technique that harnesses non-linear laser-material interactions to modify the fused silica fiber cladding. A fiber mounting and alignment technique was developed along with oil-immersion focusing to address the strong aberrations caused by the cylindrical fiber shape. The development of real-time device monitoring during the FLDW was instrumental to overcome the acute coupling sensitivity to laser alignment errors of ±1 μm positional uncertainty, and thereby opened a new practical direction for the precise fabrication of optical devices inside optical fibers. These powerful and flexible laser fabrication and characterization techniques were successfully employed to optimize optical waveguiding devices positioned within the core and cladding of optical fibers. X-, S-Bend, and directional couplers were developed to enable efficient coupling between the laser-formed cladding devices and the pre-existing core waveguide, enabling up to
An Integral Equation Representation for Overlapping Generations in Continuous Time

This paper develops a method for solving for the dynamic general equilibrium of a deterministic continuous time overlapping generations model with a finite-horizon life-cycle. The model has isoelastic preferences and allows for general assumptions about individual endowments and demographics. Solving for an equilibrium reduces to solving a nonlinear integral equation. In the special case of log utility, the integral equation is linear and global approximations to a solution are easily computed with linear algebra.
Packet Drop Rate and Round Trip Time Analysis of TCP Congestion Control Algorithm in a Cloud Based Collaborative Virtual Environment

Collaborative Virtual Environment (CVE) has become popular in the last few years. In CVE the state of the virtual objects is witnessing rapid change. When a user performs an action in CVE, the information of the action needs to be transmitted to other users to maintain consistency in the cooperative work. Currently, in the design of most CVE systems, TCP is used for its reliability. When packet loss and round trip time are high during data transmission, it affects the performance of the CVE systems. This result to inconsistent state of virtual world even with the later retransmission of the lost packets. This paper implements a cloud based architecture for improving consistency and scalability in CVE systems proposed by Gital et al. (2014). We analyze and compares the drop rate and RTT of different TCP variants with CVE architecture. Our simulation results show that Vegas, New Reno and Reno can be promising TCP variants in the cloud based CVE systems compared to other variants. The Vegas, New Reno and Reno can effectively be used as an alternative to other variants of the TCP in efficient applications of the CVE.
Anthropological and Radiographic Comparison of Vertebrae for Identification of Decomposed Human Remains

ABSTRACT: This case study demonstrates the importance of involving an anthropologist in forensic situations with decomposed remains. Anthropological consultation was used in conjunction with the comparison of antemortem and postmortem radiographs to establish positive identification of unknown, decomposed remains. The remains had no traditional identifying features such as fingerprints or dental. Through anthropological analysis, it was determined the decedent was male, between 20 and 23 years at time of death and c. 5′2″ tall. This information allowed for a presumptive identification and a request for antemortem radiographs. The missing person was identified comparing the spinous processes of the cervical and thoracic vertebrae between ante‐ and postmortem radiographs.
Phenylephrine-induced elevations in arterial blood pressure are attenuated in heat-stressed humans.

To test the hypothesis that phenylephrine-induced elevations in blood pressure are attenuated in heat-stressed humans, blood pressure was elevated via steady-state infusion of three doses of phenylephrine HCl in 10 healthy subjects in both normothermic and heat stress conditions. Whole body heating significantly increased sublingual temperature by ~0.5 degrees C, muscle sympathetic nerve activity (MSNA), heart rate, and cardiac output and decreased total peripheral vascular resistance (TPR; all P < 0.005) but did not change mean arterial blood pressure (MAP; P > 0.05). At the highest dose of phenylephrine, the increase in MAP and TPR from predrug baselines was significantly attenuated during the heat stress [DeltaMAP 8.4 +/- 1.2 mmHg; DeltaTPR 0.96 +/- 0.85 peripheral resistance units (PRU)] compared with normothermia (DeltaMAP 15.4 +/- 1.4 mmHg, DeltaTPR 7.13 +/- 1.18 PRU; all P < 0.001). The sensitivity of baroreflex control of MSNA and heart rate, expressed as the slope of the relationship between MSNA and diastolic blood pressure, as well as the slope of the relationship between heart rate and systolic blood pressure, respectively, was similar between thermal conditions (each P > 0.05). These data suggest that phenylephrine-induced elevations in MAP are attenuated in heat-stressed humans without affecting baroreflex control of MSNA or heart rate.
Anxiety activating virtual environments for investigating social phobias

Social phobia has become one of the commonest manifestations of fear in any society. This fear is often accompanied by major depression or social disabilities. With the awareness that fear can be aggravated in social situations, virtual reality researchers and psychologists have investigated the feasibility of a virtual reality system as a psychotherapeutic intervention to combat social phobia. Virtual reality technology has rapidly improved over the past few years, making for better interactions. Nevertheless, the field of virtual reality exposure therapy for social phobia is still in its infancy and various issues have yet to be resolved or event uncovered. The key concept of virtual reality exposure therapy in the treatment of social phobia is based on its characteristic of perceptual illusion - the sense of presence - as an anxiety-activating system, instead of conventional imaginal or in-vivo exposure techniques. Therefore, in order to provoke a significant level of anxiety in virtual environments, it is very important to understand the impact of perceptual presence factors in virtual reality exposure therapy. Hence, this research mainly aims to investigate all the aspects of the correlation between anxiety and the components of the virtual environment in a computer-generated social simulation. By understanding this, this thesis aims to provide a framework for the construction of effective virtual reality exposure therapy for social phobia care which enables anxiety stimuli to be controlled in a gradual manner as a conventional clinical approach. This thesis presents a series of experimental studies that have been conducted with a common theme: the function of 3D inhabitants and visual apparatus in anxiety-activating virtual social simulation, a job-interview. However, each study is conducted using different research objectives. The experimental results are presented in this thesis, with psycho-physiological approach, revealing a variation of the distribution of participants' anxiety states across various VR conditions. The overall conclusion of this research is that an appropriate realism of VR stimuli is essential in sustaining the state of anxiety over the course of VR exposure. The high fidelity of virtual environment generally provoke a greater degree of anxiety, but this research also shows that aspects of VR fidelity is more related to the mental representation of individuals to the context of the stressful situation rather than any technology that is being used.