Miracle-dz/UniFAR-FTUs huggingface dataset:
Reactivation of Latent Tuberculosis: Variations on the Cornell Murine Model

ABSTRACT Mycobacterium tuberculosis causes active tuberculosis in only a small percentage of infected persons. In most cases, the infection is clinically latent, although immunosuppression can cause reactivation of a latent M. tuberculosis infection. Surprisingly little is known about the biology of the bacterium or the host during latency, and experimental studies on latent tuberculosis suffer from a lack of appropriate animal models. The Cornell model is a historical murine model of latent tuberculosis, in which mice infected with M. tuberculosis are treated with antibiotics (isoniazid and pyrazinamide), resulting in no detectable bacilli by organ culture. Reactivation of infection during this culture-negative state occurred spontaneously and following immunosuppression. In the present study, three variants of the Cornell model were evaluated for their utility in studies of latent and reactivated tuberculosis. The antibiotic regimen, inoculating dose, and antibiotic-free rest period prior to immunosuppression were varied. A variety of immunosuppressive agents, based on immunologic factors known to be important to control of acute infection, were used in attempts to reactivate the infection. Although reactivation of latent infection was observed in all three variants, these models were associated with characteristics that limit their experimental utility, including spontaneous reactivation, difficulties in inducing reactivation, and the generation of altered bacilli. The results from these studies demonstrate that the outcome of Cornell model-based studies depends critically upon the parameters used to establish the model.
Weight-Bearing Dorsiflexion Range of Motion and Landing Biomechanics in Individuals With Chronic Ankle Instability.

CONTEXT People with chronic ankle instability (CAI) exhibit less weight-bearing dorsiflexion range of motion (ROM) and less knee flexion during landing than people with stable ankles. Examining the relationship between dorsiflexion ROM and landing biomechanics may identify a modifiable factor associated with altered kinematics and kinetics during landing tasks. OBJECTIVE To examine the relationship between weight-bearing dorsiflexion ROM and single-legged landing biomechanics in persons with CAI. DESIGN Cross-sectional study. SETTING Laboratory. PATIENTS OR OTHER PARTICIPANTS Fifteen physically active persons with CAI (5 men, 10 women; age = 21.9 ± 2.1 years, height = 168.7 ± 9.0 cm, mass = 69.4 ± 13.3 kg) participated. INTERVENTION(S) Participants performed dorsiflexion ROM and single-legged landings from a 40-cm height. Sagittal-plane kinematics of the lower extremity and ground reaction forces (GRFs) were captured during landing. MAIN OUTCOME MEASURE(S) Static dorsiflexion was measured using the weight-bearing-lunge test. Kinematics of the ankle, knee, and hip were observed at initial contact, maximum angle, and sagittal displacement. Sagittal displacements of the ankle, knee, and hip were summed to examine overall sagittal displacement. Kinetic variables were maximum posterior and vertical GRFs normalized to body weight. We used Pearson product moment correlations to evaluate the relationships between dorsiflexion ROM and landing biomechanics. Correlations (r) were interpreted as weak (0.00-0.40), moderate (0.41-0.69), or strong (0.70-1.00). The coefficient of determination (r(2)) was used to determine the amount of explained variance among variables. RESULTS Static dorsiflexion ROM was moderately correlated with maximum dorsiflexion (r = 0.49, r(2) = 0.24), ankle displacement (r = 0.47, r(2) = 0.22), and total displacement (r = 0.67, r(2) = 0.45) during landing. Dorsiflexion ROM measured statically and during landing demonstrated moderate to strong correlations with maximum knee (r = 0.69-0.74, r(2) = 0.47-0.55) and hip (r = 0.50-0.64, r(2) = 0.25-0.40) flexion, hip (r = 0.53-0.55, r(2) = 0.28-0.30) and knee (r = 0.53-0.70, r(2) = 0.28-0.49) displacement, and vertical GRF (-0.47- -0.50, r(2) = 0.22-0.25). CONCLUSIONS Dorsiflexion ROM was moderately to strongly related to sagittal-plane kinematics and maximum vertical GRF during single-legged landing in persons with CAI. Persons with less dorsiflexion ROM demonstrated a more erect landing posture and greater GRF.
Tools for supporting cooperative work near and far: highlights from the CSCW conference

The second conference on Computer Supported Cooperative Work has provided focus on use of computers for supporting workers that are at various levels of geographic dispersion. The participants in this panel reported case studies at that conference on group work (1) in face-to-face meetings, (2) in the same building, and (3) distributed across a number of sites. Each panelist therefore brings insight about the communication needs of their research subjects and both the value and limitations of particular technologies for supporting the communication that ties the members of the groups together as geographic distance varies. Each of the panelists will address the following two questions:What are the preferred types of communication (visual, written, spoken) for people working together at particular geographic distances? What are the benefits and shortcomings of available technologies (video, electronic-mail, telephone/voice mail) for supporting these types of communication?
FlexProt: Alignment of Flexible Protein Structures Without a Predefinition of Hinge Regions

FlexProt is a novel technique for the alignment of flexible proteins. Unlike all previous algorithms designed to solve the problem of structural comparisons allowing hinge-bending motions, FlexProt does not require an a priori knowledge of the location of the hinge(s). FlexProt carries out the flexible alignment, superimposing the matching rigid subpart pairs, and detects the flexible hinge regions simultaneously. A large number of methods are available to handle rigid structural alignment. However, proteins are flexible molecules, which may appear in different conformations. Hence, protein structural analysis requires algorithms that can deal with molecular flexibility. Here, we present a method addressing specifically a flexible protein alignment task. First, the method efficiently detects maximal congruent rigid fragments in both molecules. Transforming the task into a graph theoretic problem, our method proceeds to calculate the optimal arrangement of previously detected maximal congruent rigid fragments. The fragment arrangement does not violate the protein sequence order. A clustering procedure is performed on fragment-pairs which have the same 3-D rigid transformation regardless of insertions and deletions (such as loops and turns) which separate them. Although the theoretical worst case complexity of the algorithm is O(n(6)), in practice FlexProt is highly efficient. It performs a structural comparison of a pair of proteins 300 amino acids long in about seven seconds on a standard desktop PC (400 MHz Pentium II processor with 256MB internal memory). We have performed extensive experiments with the algorithm. An assortment of these results is presented here. FlexProt can be accessed via WWW at bioinfo3d.cs. tau.ac. il/FlexProt/.
Fria: fast and robust instance alignment

This paper proposes Fria, a fast and robust instance alignment framework across two independently built knowledge bases (KBs). Our objective is two-fold: (1) to design an effective instance similarity measure and (2) to build a fast and robust alignment framework. Specifically, Fria consists of two-phases. Fria first achieves high-precision alignment for seed matches which have strong evidence for aligning. To obtain high-recall alignment, Fria then divides non-matched instances according to the types identified from seeds, and gives additional chances to the same-typed instances to be matched. Experimental results show that Fria is fast and robust, by achieving comparable accuracy to state-of-the-arts and a 10-times speed up.
Interaction refinement in the design of business collaborations

To tackle the complexity of inter-organizational business collaborations, the design of such collaborations may require explicit modelling at multiple abstraction levels. At a high abstraction level, the collaboration is specified as a single abstract interaction; and at a lower abstraction level, the collaboration is specified as a composition of more-concrete interactions. Interaction refinement is a design operation in which an abstract interaction is replaced with multiple related more-concrete interactions. The availability of an interaction design concept that is suitable for modelling interactions at multiple abstraction levels would facilitate the refinement. Supporting design operations are necessary to check whether an interaction refinement is correct or conforms to the abstract interaction it replaces. This paper presents an interaction design concept and associated operations to support the design of business collaborations at successive abstraction levels.
Pulmonary Nodules: growth rate assessment in patients by using serial CT and three-dimensional volumetry.

PURPOSE To determine the precision of a three-dimensional (3D) method for measuring the growth rate of solid and subsolid nodules and its ability to detect abnormal growth rates. MATERIALS AND METHODS This study was approved by the Institutional Research Board and was HIPAA compliant. Informed consent was waived. The growth rates of 123 lung nodules in 59 patients who had undergone lung cancer screening computed tomography (CT) were measured by using a 3D semiautomated computer-assisted volume method. Clinical stability was established with long-term CT follow-up (mean, 6.4 years±1.9 [standard deviation]; range, 2.0-8.5 years). A mean of 4.1 CT examinations per patient±1.2 (range, two to seven CT examinations per patient) was analyzed during 2.4 years±0.5 after baseline CT. Nodule morphology, attenuation, and location were characterized. The analysis of standard deviation of growth rate in relation to time between scans yielded a normative model for detecting abnormal growth. RESULTS Growth rate precision increased with greater time between scans. Overall estimate for standard deviation of growth rate, on the basis of 939 growth rate determinations in clinically stable nodules, was 36.5% per year. Peripheral location (P=.01; 37.1% per year vs 25.6% per year) and adjacency to pleural surface (P=.05; 38.9% per year vs 34.0% per year) significantly increased standard deviation of growth rate. All eight malignant nodules had an abnormally high growth rate detected. By using 3D volumetry, growth rate-based diagnosis of malignancy was made at a mean of 183 days±158, compared with radiologic or clinical diagnosis at 344 days±284. CONCLUSION A normative model derived from the variability of growth rates of nodules that were stable for an average of 6.4 years may enable identification of lung cancer.
An IoT infrastructure for ubiquitous notifications in intelligent living environments

Notifications are an important feature to proactively inform smartphone users. However, reading notifications on phones often has a disruptive effect on tasks at hand or social situations. Today's smart home and office environments with their increasingly connected devices provide rich opportunities to deliver notifications in a context-sensitive and multi-modal way into the direct surroundings of a user eliminating the need to fish up the smartphone from the pocket. Due to the missing tool support these opportunities have however neither been sufficiently investigated nor picked up for use in daily lives. With this work we introduce an infrastructure for homes and offices that enables designers and web-developers to design and deploy context sensitive notification strategies using arbitrary connected things and smart home products such as TVs, tablets, projections, lamps, speakers and many more. We introduce the opportunities offered by this platform to go beyond simple Event-Condition-Rules and describe how the system can be used to carry out remotely controlled "in the wild" experiments.
Curcumin Regulates Expression and Activity of Matrix Metalloproteinases 9 and 2 during Prevention and Healing of Indomethacin-induced Gastric Ulcer*

Matrix metalloproteinases (MMPs) are suggested to play a critical role in extracellular matrix degradation and remodeling during inflammation and wound healing processes. However, the role of MMPs in indomethacin-induced gastric ulcer and its healing process are not clearly understood. This study is aimed at determining the regulation of MMP-9 and -2 activities in indomethacin-induced acute gastric ulceration and healing. Indomethacin-ulcerated stomach extracts exhibit significant up-regulation of pro-MMP-9 (92 kDa) activity and moderate reduction of MMP-2 activity, which strongly correlate with indomethacin dose and severity of ulcer. The anti-inflammatory and antioxidant properties of curcumin, an active component of turmeric, suggest that curcumin may exert antiulcer activity through scavenging reactive oxygen species, by regulating MMP activity, or both. To test these possibilities, the effect of curcumin in indomethacin-induced gastric ulcer is examined by biochemical and histological methods. The results show that curcumin exhibits potent antiulcer activity in acute ulcer in rat model by preventing glutathione depletion, lipid peroxidation, and protein oxidation. Denudation of epithelial cells during damage of gastric lumen is reversed by curcumin through re-epithelialization. Furthermore, both oral and intraperitoneal administration of curcumin blocks gastric ulceration in a dose-dependent manner. It accelerates the healing process and protects gastric ulcer through attenuation of MMP-9 activity and amelioration of MMP-2 activity. Omeprazole, an established antiulcer drug does not inhibit MMP-9 while protecting indomethacin-induced gastric ulcer. We conclude that antiulcer activity of curcumin is primarily attributed to MMP-9 inhibition, one of the major path-ways of ulcer healing.
Novel Saccharomyces cerevisiae Screen Identifies WR99210 Analogues That Inhibit Mycobacterium tuberculosis Dihydrofolate Reductase

ABSTRACT The ongoing selection of multidrug-resistant strains of Mycobacterium tuberculosis has markedly reduced the effectiveness of the standard treatment regimens. Thus, there is an urgent need for new drugs that are potent inhibitors of M. tuberculosis, that exhibit favorable resistance profiles, and that are well tolerated by patients. One promising drug target for treatment of mycobacterial infections is dihydrofolate reductase (DHFR; EC 1.5.1.3), a key enzyme in folate utilization. DHFR is an important drug target in many pathogens, but it has not been exploited in the search for drugs effective against M. tuberculosis. The triazine DHFR inhibitor WR99210 has been shown to be effective against other mycobacteria. We show here that WR99210 is also a potent inhibitor of M. tuberculosis and Mycobacterium bovis BCG growth in vitro and that resistance to WR99210 occurred less frequently than resistance to either rifampin or isoniazid. Screening of drugs with M. tuberculosis cultures is slow and requires biosafety level 3 facilities and procedures. We have developed an alternative strategy: initial screening in an engineered strain of the budding yeast Saccharomyces cerevisiae that is dependent on the M. tuberculosis DHFR for its growth. Using this system, we have screened 19 compounds related to WR99210 and found that 7 of these related compounds are also potent inhibitors of the M. tuberculosis DHFR. These studies suggest that compounds of this class are excellent potential leads for further development of drugs effective against M. tuberculosis.
Signaling through BMP type 1 receptors is required for development of interneuron cell types in the dorsal spinal cord

During spinal cord development, distinct classes of interneurons arise at stereotypical locations along the dorsoventral axis. In this paper, we demonstrate that signaling through bone morphogenetic protein (BMP) type 1 receptors is required for the formation of two populations of commissural neurons, DI1 and DI2, that arise within the dorsal neural tube. We have generated a double knockout of both BMP type 1 receptors, Bmpr1a and Bmpr1b, in the neural tube. These double knockout mice demonstrate a complete loss of D1 progenitor cells, as evidenced by loss of Math1 expression, and the subsequent failure to form differentiated DI1 interneurons. Furthermore, the DI2 interneuron population is profoundly reduced. The loss of these populations of cells results in a dorsal shift of the dorsal cell populations, DI3 and DI4. Other dorsal interneuron populations, DI5 and DI6, and ventral neurons appear unaffected by the loss of BMP signaling. The Bmpr double knockout animals demonstrate a reduction in the expression of Wnt and Id family members, suggesting that BMP signaling regulates expression of these factors in spinal cord development. These results provide genetic evidence that BMP signaling is crucial for the development of dorsal neuronal cell types.
Cooperative Action of the Catabolite Activator Protein and AraC In Vitro at the araFGH Promoter

ABSTRACT Full activation of transcription of the araFGHpromoter, pFGH, requires both the catabolite activator protein (CAP) and AraC protein. AtpFGH, the binding site for CAP is centered at position −41.5, an essential binding site for AraC is centered at position −79.5, and a second, nonessential binding site is centered at position −154.5. In this work, we used the minimal promoter region required for in vivo activation of pFGH to examine the roles of CAP and AraC in stimulating formation of open complexes at pFGH. Migration retardation assays of open complexes showed that RNA polymerase binds exceptionally tightly to the AraC-CAP-pFGH complex and that the order of addition of proteins to the initiating complex is important. Similar assays with RNA polymerase containing truncated alpha subunits suggest that AraC interacts with the C-terminal domain of the alpha subunit. Finally, AraC protein also acts to prevent the improper binding of RNA polymerase at a pseudo promoter near the truepFGH promoter.
Spatial encoding using a code division technique for fast ultrasound imaging

This paper describes a method for spatial encoding in synthetic transmit aperture ultrasound imaging. This allows several ultrasonic sources to be active simultaneously. The method is based on transmitting pseudorandom sequences to spatially encode the transmitters. The data can be decoded after only one transmission using the knowledge of the transmitted code sequences as opposed to other spatial encoding techniques, such as Hadamard or Golay encoding. This makes the method less sensitive to motion, and data can be acquired using fewer transmissions. The aim of this paper is to analyze the underlying theory and to test the feasibility in a physical system. The method has been evaluated in simulations using Field II in which the point-spread functions were simulated for different depths for a 7 MHz linear array transducer. A signal-to-noise ratio (SNR) simulation also was included in the study in which an improvement in SNR of ~1.5 dB was attained compared to the standard synthetic transmit aperture (STA) firing scheme. Considering the amount of energy transmitted, this value is low. A plausible explanation is given that is verified in simulation. The method also was tested in an experimental ultrasound scanner and compared to a synthetic transmit aperture ultrasound imaging scheme using a sinusoidal excitation. The performance of the proposed method was comparable to the reference with respect to axial and lateral resolution, but it displayed poorer contrast with sidelobe levels at ~ - 40 dB compared to the mainlobe.
Noise sustained propagation: local versus global noise

We expand on prior results on noise supported signal propagation in arrays of coupled bistable elements. We present and compare experimental and numerical results for kink propagation under the influence of local and global fluctuations. As demonstrated previously for local noise, an optimum range of global noise power exists for which the medium acts as a reliable transmission "channel. " We discuss implications for propagation failure in a model of cardiac tissue, and present a general theoretical framework based on discrete kink statistics. Valid for generic bistable chains, the theory captures the essential features observed in our experiments and numerical simulations.
An analysis of postoperative thigh symptoms after minimally invasive transpsoas lumbar interbody fusion.

OBJECTIVE The minimally invasive transpsoas interbody fusion technique requires dissection through the psoas muscle, which contains the nerves of the lumbosacral plexus posteriorly and genitofemoral nerve anteriorly. Retraction of the psoas is becoming recognized as a cause of transient postoperative thigh pain, numbness, paresthesias, and weakness. However, few reports have described the nature of thigh symptoms after this procedure. METHODS The authors performed a review of patients who underwent the transpsoas technique for lumbar spondylotic disease, disc degeneration, and spondylolisthesis treated at a single academic medical center. A review of patient charts, including the use of detailed patient-driven pain diagrams performed at equal preoperative and follow-up intervals, investigated the survival of postoperative thigh pain, numbness, paresthesias, and weakness of the iliopsoas and quadriceps muscles in the follow-up period on the ipsilateral side of the surgical approach. RESULTS Over a 3.2-year period, 59 patients underwent transpsoas interbody fusion surgery. Of these, 62.7% had thigh symptoms postoperatively. New thigh symptoms at first follow-up visit included the following: burning, aching, stabbing, or other pain (39.0%); numbness (42.4%); paresthesias (11.9%); and weakness (23.7%). At 3 months postoperatively, these percentages decreased to 15.5%, 24.1%, 5.6%, and 11.3%, respectively. Within the patient sample, 44% underwent a 1-level, 41% a 2-level, and 15% a 3-level transpsoas operation. While not statistically significant, thigh pain, numbness, and weakness were most prevalent after L4-5 transpsoas interbody fusion at the first postoperative follow-up. The number of lumbar levels that were surgically treated had no clear association with thigh symptoms but did correlate directly with surgical time, intraoperative blood loss, and length of hospital stay. CONCLUSIONS Transpsoas interbody fusion is associated with high rates of immediate postoperative thigh symptoms. While larger, prospective studies are necessary to validate these findings, the authors found that half of the patients had symptom resolution at approximately 3 months postoperatively and more than 90% by 1 year.
Atmospheric pressure chemical ionization mass spectrometry of pyridine and isoprene: potential breath exposure and disease biomarkers

Volatile organic compounds (VOCs) in exhaled human breath can serve as potential disease-specific and exposure biomarkers and therefore can reveal information about a subject's health and environment. Pyridine, a VOC marker for exposure to tobacco smoke, and isoprene, a liver disease biomarker, were studied using atmospheric pressure chemical ionization mass spectrometry (APCI-MS). While both molecules could be detected in low-ppb levels, interactions of the ionized analytes with their neutral forms and ambient air led to unusual ion/molecule chemistry. The result was a highly dynamic system and a nonlinear response to changes in analyte concentration. Increased presence of ambient water was found to greatly enhance the detection limit of pyridine and only slightly decrease that of isoprene. APCI-MS is shown to be a promising analytical tool in breath analysis with good detection limits, but its application requires a better understanding of the ion/molecule chemistry that may affect VOC quantification from a chemically complex system such as human breath.