Miracle-dz/UniFAR-FTUs huggingface dataset:
Cassette Dosing Approach and Quantitative Structure-Pharmacokinetic Relationship Study of Antifungal N-Myristoyltransferase Inhibitors

Pharmacokinetic (PK) parameters of N-myristoyltransferase (Nmt) inhibitors were measured, and a multivariate quantitative structure-pharmacokinetic relationship (QSPKR) model for predicting rat elimination half-life (t(1/2)) values was constructed. One hundred seven benzofuran derivatives have been selected as the data set for QSPKR analysis. The correlation between the t(1/2) values and 30 physicochemical descriptors was examined by a stepwise multiple linear regression method. The statistical analysis gives a significant QSPKR model (r = 0.843) with the following three variables: partial negative surface area (PNSA), atomic-based octanol/water partition coefficient (AlogP), and the number of rotational bonds (Rotlbonds). The QSPKR model obtained is predictive and simple, and would give a direction for designing new Nmt inhibitors having good PK profiles.
Evolution of breeding systems and fruits in New World Galium and relatives (Rubiaceae).

UNLABELLED PREMISE OF THE STUDY Dioecy occurs in only about 6% of angiosperms, yet it has evolved many times from hermaphroditism. Polygamy is an even more uncommon condition within angiosperms, in which both unisexual and bisexual flowers occur within a species. Polygamy, dioecy, and hermaphroditism all occur within a New World clade of Galium (Rubiaceae), in which dioecy is hypothesized to have evolved from hermaphroditism via polygamy. At least five sections of Galium as traditionally defined by fruit morphology occur within this group. We tested the monophyly of sections defined by fruit morphology and sought to determine origins and pathways of breeding systems within this group. • METHODS We obtained chloroplast (rpoB-trnC, trnC-psbM, trnL-ndhJ) and nuclear ribosomal (external transcribed spacer) DNA sequences for 89 taxa from the Cruciata-Galium-Valantia (CGV) clade to estimate the phylogeny. Ancestral states for breeding systems, fruit types, and fruit hairs were reconstructed using parsimony and likelihood analyses. • KEY RESULTS We identified nine well-supported lineages of New World Galium taxa. However, none of the sections traditionally defined by fruit morphology are monophyletic. Dioecy is inferred to have arisen at least three times from hermaphroditism; polygamy is inferred to have arisen at least twice from dioecy and at least six times from hermaphroditism. • CONCLUSIONS Polygamy appears to be a terminal condition in the CGV clade and not a pathway to dioecy. Fruit characters traditionally used in the taxonomy of this group have arisen multiple times within this clade of Galium and are not reliable indicators of shared evolutionary history.
Trauma Pervasively Elevates Brief Symptom Inventory Profiles in Inpatient Women

The Brief Symptom Inventory was administered to 228 women (M age: 37) consecutively admitted to specialized inpatient treatment for trauma-related disorders. Subsamples of patients were administered different posttraumatic stress disorder scales, the Impact of Events Scale–Revised, the Posttraumatic Stress Diagnostic Scale, and the PTSD scale of the Millon Clinical Multiaxial Inventory–Ill, as well as a measure of child abuse and neglect, the Childhood Trauma Questionnaire. In this severely traumatized group, every scale of the Brief Symptom Inventory was significantly more elevated than the inpatient female norms, with the five most highly elevated scales being Depression, Obsessive-Compulsive, Anxiety, Interpersonal Sensitivity, and Psychoticism. Different indicators of trauma (Childhood Trauma Questionnaire, PTSD scales, and PTSD diagnosis) show different patterns of relationships with the individual scales of the Brief Symptom Inventory. There is no simple relationship between trauma and BSI symptoms, but clinicians should consider severe interpersonal trauma to be one pathway to pervasively elevated profiles of the Brief Symptom Inventory.
An energy efficient joint energy beamforming and time allocation with QoS guarantee via wireless energy transfer

Wireless energy transfer (WET) has been considered as a promising technology for providing mobile devices with untethered energy supply in wireless networks. In this paper, we assume one energy supplier (ES) and multiple WET powered terminals coexist. The ES wirelessly charge the terminals, and then terminals transfer their own information synchronously. The WET broadcast and wireless information transfer (WIT) take place in time duplexing manner. The WET powered terminals are assumed to have individual quality of service (QoS) requirements of information transfer. The joint design of downlink WET broadcast beamforming and time allocation between energy/information transfer is studied. An two step algorithm is proposed to jointly design both time duplexing factor and beamforming vector, in order to guarantee the terminals' QoS, meanwhile to minimize the WET power consumption by WET. To avoid iterative search, proposed algorithm first determine the time allocating factor by minimizing the lower bound of WET power. Then the optimal WET beamforming vector is obtained to guarantee terminals' QoS. Simulation results demonstrates proposed algorithm provides majority of the performance of global optimal solution while avoiding the computational burden of iterative optimization.
A Balanced Approach to Capturing User Requirements in Business- to- Consumer Web Information Systems

The development of business-to-consumer web information systems pose special challenges in the requirements analysis phase. It is difficult to capture user requirements given that users are relatively autonomous and anonymous and there are no major incentives for users to become involved in the development of a web information system. The researchers reviewed traditional requirement elicitation techniques, marketing research techniques and web usage analysis techniques. Current practice was assessed and the findings suggest that a balanced approach to user requirements capture will result in more complete and user centred requirements. This approach should lead to more effective business-to consumer web information systems.
Doxorubicin with cyclophosphamide followed by docetaxel every 21 days compared with doxorubicin and docetaxel every 14 days as preoperative treatment in operable breast cancer: the GEPARDUO study of the German Breast Group.

PURPOSE Dose-dense and sequential administration of cytotoxic drugs are current approaches to improve outcomes in patients with early-stage breast cancer. METHODS This phase III study investigated 913 women with untreated operable breast cancer (T2-3, N0-2, M0) randomly assigned to receive either doxorubicin 50 mg/m2 plus docetaxel 75 mg/m2 every 14 days for four cycles with filgrastim support (ADOC), or doxorubicin 60 mg/m2 plus cyclophosphamide 600 mg/m2 every 21 days followed by docetaxel 100 mg/m2 every 21 days for four cycles each (AC-DOC). The primary end point was the incidence of pathologic complete (invasive and noninvasive) response (pCR) in the breast and axillary nodes. Secondary end points were predictors for pCR, clinical response, rate of breast conservation, and safety. RESULTS A pCR was achieved in 94 patients (10.6%), but the likelihood was significantly greater with AC-DOC (14.3%; n = 63) than with ADOC (7.0%; n = 31) (odds ratio, 2.22; 90% CI, 1.52 to 3.24; P < .001). Independent predictors of attaining a pCR included the use of sequential therapy, high tumor grade, and negative hormone receptor status. The response rates detected by palpation and by imaging were significantly higher with AC-DOC (85.0% and 78.6%, respectively) than with ADOC (75.2% and 68.6%, respectively; both P values < .001). The rate of breast-conserving surgery was 63.4% for AC-DOC and 58.1% for ADOC (P = .05). Predominant grade 3/4 toxicities were leucopenia (AC-DOC, 74.2%; ADOC, 53.7%) and neutropenia (AC-DOC, 66.4%; ADOC, 44.7%) but were infrequently associated with fever (AC-DOC, 4.6%; ADOC, 3.1%). CONCLUSION Sequential AC-DOC is more effective at inducing pCR than dose-dense ADOC as preoperative treatment for patients with operable breast cancer.
Cultural Heritage Layers: Integrating Historic Media in Augmented Reality

In this paper we are presenting Cultural Heritage Layers, an approach that enables the visualization of historic media like drawings, paintings and photographs of buildings and historic scenes seamlessly superimposed on reality via video see through using X3D. This enables simple, inexpensive and sustainable Augmented Reality applications in the cultural heritage and architectural area based on industry standards. The main idea is to use existing historic media from archives and superimpose them seamlessly on reality at the right spot. These locative layers are context sensitively telling the location's history and create the impression of a virtual time journey. The registration of the virtual objects in the video images is provided by a robust 6DOF tracking framework based on two technologies that work in tandem: an initialization step based on Randomized Trees and a frame-to-frame tracking phase based on KLT. The entire application runs in real time on current Ultra Mobile PCs and MIDs.
Vertebral augmentation by kyphoplasty and vertebroplasty: 8 years experience outcomes and complications

Background and Context: Minimally invasive percutaneous vertebral augmentation techniques; vertebroplasty, and kyphoplasty have been treatment choices for vertebral compression fractures (VCFs). The purpose of this study is to evaluate the outcomes of the patients who underwent vertebroplasty or kyphoplasty regarding complications, correction of vertebral body height, kyphosis angle and pain relief assessment using visual analog score (VAS) for pain. Materials and Methods: A retrospective review of the hospital records for 100 consecutive patients treated with kyphoplasty or vertebroplasty in our department database. Patients with osteoporotic compression fractures, traumatic compressions, and osteolytic vertebral lesions, including metastases, hemangiomas, and multiple myeloma, were included in the study. Preoperative and postoperative VAS pain scores, percentages of vertebral compression and kyphotic angles were measured and compared as well as demographic characteristics and postoperative complications. Mobilization and length of stay (LOS) were recorded. Results: One hundred patients were treated by 110 procedures. 64 patients were operated on due to osteoporosis (72 procedures). Twelve patients were operated on because of metastasis (13 procedures), 8 patients were operated on because of multiple myeloma (9 procedures). Five patients had two surgeries, 1 patient had 3 surgeries, and 1 patient had 5 surgeries. The mean preoperative VAS was 74.05 ± 9.8. In total, 175 levels were treated, 46 levels by kyphoplasty and 129 by vertebroplasty. The mean postoperative VAS was 20.94 ± 11.8. Most of the patients were mobilized in the same day they of surgery. Mean LOS was 1.83 days. Six patients had nonsymptomatic leakage of polymethlymethacrylate, and patient had epidural hematoma, which was operated on performing hemi-laminectomy. Conclusions: Percutaneous vertebroplasty and balloon kyphoplasty are both effective and safe minimally invasive procedures for the stabilization of VCFs. However, complications should be kept in mind during decision making.
Effect of an N‐terminus deletion on voltage‐dependent gating of the ClC‐2 chloride channel

ClC‐2, a chloride channel widely expressed in mammalian tissues, is activated by hyperpolarisation and extracellular acidification. Deletion of amino acids 16‐61 in rat ClC‐2 abolishes voltage and pH dependence in two‐electrode voltage‐clamp experiments in amphibian oocytes. These results have been interpreted in terms of a ball‐and‐chain type of mechanism in which the N‐terminus would behave as a ball that is removed from an inactivating site upon hyperpolarisation. We now report whole‐cell patch‐clamp measurements in mammalian cells showing hyperpolarization‐activation of rClC‐2Δ16‐61 differing only in presenting faster opening and closing kinetics than rClC‐2. The lack of time and voltage dependence observed previously was reproduced, however, in nystatin‐perforated patch experiments. The behaviour of wild‐type rClC‐2 did not differ between conventional and nystatin‐perforated patches. Similar results were obtained with ClC‐2 from guinea‐pig. One possible explanation of the results is that some diffusible component is able to lock the channel in an open state but does so only to the mutated channel. Alternative explanations involving the osmotic state of the cell and cytoskeleton structure are also considered. Low extracellular pH activates the wild‐type channel but not rClC‐2Δ16‐61 when expressed in oocytes, a result that had been interpreted to suggest that protons affect the ball‐and‐chain mechanism. In our experiments no difference was seen in the effect of extracellular pH upon rClC‐2 and rClC‐2Δ16‐61 in either recording configuration, suggesting that protons act independently from possible effects of the N‐terminus on gating. Our observations of voltage‐dependent gating of the N‐terminal deleted ClC‐2 are an argument against a ball‐and‐chain mechanism for this channel.
Magnetic Measurements and Analysis of the First 11-T Nb$_3$ Sn 2-in-1 Model for HL-LHC

In the framework of the High-Luminosity upgrade of the Large Hadron Collider, the design and development of new magnets, relying on Nb$_3$Sn superconducting cables, is progressing. In particular, a double-aperture dipole, with a bore diameter of 60 mm and a central field of 11 T, is required for the replacement of some Nb–Ti dipoles in the dispersion suppressor areas. The new magnets must comply with the specifications of the machine in terms of reliability and field quality. An intense short-model campaign was launched in order to validate the design choices. Various single-aperture models have been built and tested. Recently, the first 2-in-1 model has been produced by assembling the collared coils already tested in the single-aperture configuration. This paper presents the analysis of the magnetic measurements on the first 2-m-long, double-aperture demonstrator built and tested at CERN. The geometrical field multipoles, the iron saturation effects, the magnetic cross-talk as well as the effects of persistent currents are presented. The experimental data are compared with the magnetic calculations using the CERN field computation program ROXIE and are discussed in view of the construction of the full-length magnets.
Unique pattern of urinary tract calculi in Australian Aboriginal children

Young Aboriginal children in remote regions of tropical and desert Australia are at risk of developing urate stones in their upper urinary tract from an early age. These radiolucent calculi were only recognized with the availability of ultrasound diagnosis and are not associated with anatomic anomalies or abnormal uric acid production/metabolism. Although these stones appear to resolve spontaneously after the weaning period, some result in ureteric obstruction and infection which may lead to renal damage. This pattern of urolithiasis differs from the usual global urolithiasis pattern of either endemic bladder stones in young children in developing countries or predominantly calcium‐based stones in upper tracts of older children and adults in affluent industrialized countries, where upper tract urate stones account for only a minority of childhood urinary tract stones. Risk factors for urate stones are low urine output and acidic urine. An association between urolithiasis and carbohydrate intolerance leading to chronic acidosis has been suggested for Aboriginal children, but existing limited evidence does not support this as a major aetiological factor. Although further studies on the epidemiology, natural history and management of these urate stones are needed, we believe the focus should be on improving the known social and environmental risk factors of remote Aboriginal children during the weaning period which contribute to the unacceptably high prevalence of failure to thrive, diarrhoeal disease, environmental enteropathy, iron deficiency and urolithiasis.
Bis(mu-oxo)dicopper in Cu-ZSM-5 and its role in the decomposition of NO: a combined in situ XAFS, UV-vis-near-IR, and kinetic study.

In situ XAFS combined with UV-vis-near-IR spectroscopy are used to identify the active site in copper-loaded ZSM-5 responsible for the catalytic decomposition of NO. Cu-ZSM-5 was probed with in situ XAFS (i) after O(2) activation and (ii) while catalyzing the direct decomposition of NO into N(2) and O(2). A careful R-space fitting of the Cu K-edge EXAFS data is presented, including the use of different k-weightings and the analysis of the individual coordination shells. For the O(2)-activated overexchanged Cu-ZSM-5 sample a Cu.Cu contribution at 2.87 A with a coordination number of 1 is found. The corresponding UV-vis-near-IR spectrum is characterized by an intense absorption band at 22 700 cm(-1) and a relatively weaker band at 30 000 cm(-1), while no corresponding EPR signal is detected. Comparison of these data with the large databank of well-characterized copper centers in enzymes and synthetic model complexes leads to the identification of the bis(mu-oxo)dicopper core, i.e. [Cu(2)(mu-O)(2)](2+). After dehydration in He, Cu-ZSM-5 shows stable NO decomposition activity and the in situ XAFS data indicate the formation of a large fraction of the bis(mu-oxo)dicopper core during reaction. When the Cu/Al ratio of Cu-ZSM-5 exceeds 0.2, both the bis(mu-oxo)dicopper core is formed and the NO decomposition activity increases sharply. On the basis of the in situ measurements, a reaction cycle is proposed in which the bis(mu-oxo)dicopper core forms the product O(2) on a single active site and realizes the continuous O(2) release and concomitant self-reduction.
Comparative proteome analysis of Hansenula polymorpha DL1 and A16

Proteomic responses of methylotrophic yeasts (Hansenula polymorpha DL1 and A16) to growth medium tuning by carbon source shift (glycerol→methanol) were monitored and analyzed by two‐dimensional gel electrophoresis. Through comparative analyses of two‐dimensional gels, intracellular yeast proteins with complex expression patterns were systematically sorted into: (1) proteins that are commonly expressed with comparable high abundance in both strains; (2) strain‐specific proteins that are expressed at high level only in a particular strain; (3) strain‐specific and methanol‐induced proteins that are expressed only in the presence of methanol; and (4) strain‐specific and constitutively‐expressed proteins that are expressed consistently irrespective of carbon source shift without extreme change in expression level. Among the DL1‐specific proteins belonging to group four, the four proteins showing the highest expression levels in the course of the fermentation process were identified as: glucose‐6‐phosphate dehydrogenase, isocitrate lyase, succinyl‐CoA synthetase, and glycerol‐3‐phosphate dehydrogenase. From these results, it is suggested that DL1 has distinct metabolic characteristics including enhanced metabolic activities both in glycerol uptake and the glyoxylate bypass cycle, as compared to A16. This is likely to explain why the DL1 strain shows a significantly higher rate of glycerol and methanol consumption during the fermentation process. Our systematic approach to the analysis of proteomic responses and the detailed analysis results reported here will be useful to better understand the global physiology of H. polymorpha, as proteome databases for various methylotrophic yeasts are established.
HealthCall: Technology-based extension of motivational interviewing to reduce non-injection drug use in HIV primary care patients – a pilot study

Abstract To reduce non-injection drug use (NIDU) among HIV primary care patients, more than a single brief intervention may be needed, but clinic resources are often too limited for extended interventions. To extend brief motivational interviewing (MI) to reduce NIDU, we designed and conducted a pilot study of “HealthCall,” consisting of brief (1–3 minutes) daily patient calls reporting NIDU and health behaviors to a telephone-based interactive voice response (IVR) system, which provided data for subsequent personalized feedback. Urban HIV adult clinic patients reporting ≥4 days of NIDU in the previous month were randomized to two groups: MI-only (n=20) and MI+HealthCall (n=20). At 30 and 60 days, patients were assessed and briefly discussed their NIDU behaviors with their counselors. The outcome was the number of days patients used their primary drug in the prior 30 days. Medical marijuana issues precluded HealthCall with patients whose primary substance was marijuana (n=7); excluding these, 33 remained, of whom 28 patients (MI-only n=17; MI+HealthCall n=11) provided post-treatment data for analysis. Time significantly predicted reduction in “days used” in both groups (p<0.0001). At 60 days, between-group differences approached trend level, with an effect size of 0.62 favoring the MI+HealthCall arm. This pilot study suggests that HealthCall is feasible and acceptable to patients in resource-limited HIV primary care settings and can extend patient involvement in brief intervention with little additional staff time. A larger efficacy trial of HealthCall for NIDU-reduction in such settings is warranted.
A systematic review of the cost-effectiveness of interventions for supporting informal caregivers of people with dementia residing in the community

ABSTRACT Background: Dementia places a huge demand on healthcare services; however, a large proportion of the cost is borne by informal caregivers. With the number of people affected by dementia set to increase in the future, there is a need for research to consider the effects of interventions on informal caregivers as well as on the individuals with dementia. This paper seeks to systematically review the existing evidence on the cost-effectiveness of interventions to support informal caregivers of people with dementia residing in the community. Methods: A range of electronic databases was searched. Studies were included if both costs and outcome measures for informal caregivers of people with dementia residing in the community were reported for an intervention. Both pharmacological and non-pharmacological interventions were included. Quality of study was assessed using the Drummond ten-item checklist for economic evaluations and results were presented through narrative synthesis. Results: Twelve studies were included in the review; of these only four reported a significant difference in the outcome measure for caregivers. Conclusions: At present few published studies report costs in enough detail to provide evidence of the effectiveness and cost-effectiveness of interventions for supporting caregivers. Future trials need to collect caregiver data alongside patient data in order to increase the evidence base for intervention effectiveness. Further research is required to establish the effectiveness and cost-effectiveness of both pharmacological and non-pharmacological approaches.