Miracle-dz/UniFAR-FTUs huggingface dataset:
Molecular epidemiology and drug sensitivity pattern of Mycobacterium tuberculosis strains isolated from pulmonary tuberculosis patients in and around Ambo Town, Central Ethiopia

Introduction Tuberculosis (TB) is caused by M. tuberculosis complex and remains a major global public health problem. The epidemic remains a threat to sub-Saharan Africa, including Ethiopia, with further emergence of drug resistant TB. We investigated the drug sensitivity pattern and molecular epidemiology of mycobacterial strains isolated from pulmonary TB patients in and around Ambo town in Oromia Region, Central Ethiopia. Methods A cross-sectional study was conducted involving 105 consecutive new smear positive pulmonary TB patients diagnosed at Ambo Hospital and surrounding Health Centers between May 2014 and March 2015 upon informed consent. Sputum samples were cultured on Löwenstein-Jensen (LJ) media using standard techniques to isolate mycobacteria. Region of difference 9 (RD9)-based polymerase chain reaction (PCR) and spoligotyping was employed for the identification of the isolates at species and strain levels. The spoligotype patterns were entered into the SITVIT database to determine Octal and SIT (Spoligotyping International Typing) numbers for each strain. The sensitivity of the isolates to isoniazid (INH), rifampicin (RIF), ethambutol (ETB) and streptomycin (STM) was evaluated on LJ-medium with the indirect proportion method. Results Cultures were positive in 86/105 (82%) of newly diagnosed smear positive pulmonary TB cases. All of the 86 isolates were confirmed as M. tuberculosis. The majority (76.7%) of them were clustered into seven groups while the rest (23.3%) appeared unique. The most predominant Spoligotypes were SIT53 and SIT149, consisting of 24.4% and 20.9% of the isolates, respectively. Assigning of the isolates to family using SPOTCLUST software revealed that 45.3% of the isolates belonged to T1, 23.3% to T3 and 13% to CAS family. The majority (76.7%) of the M. tuberculosis isolates were susceptible to all the four drugs. Any resistance to any one of the four drugs was detected in 23.3% of the isolates. The highest proportion of any resistance was observed against isoniazid (9.3%) and ethambutol (7%). There was only a single case (1.2%) of multidrug resistant/rifampicin resistant (MDR/RR) TB. Conclusion The majority of the isolates were clustered suggesting on-going active transmission in the study area. Mono resistance is relatively prevalent while the magnitude of MDR/RR-TB was found to be lower than in previous studies.
Suppression of pancreatic ductal adenocarcinoma growth by intratumoral delivery of attenuated Salmonella typhimurium using a dual fluorescent live tracking system

ABSTRACT Pancreatic ductal adenocarcinoma (PDAC) has the poorest prognosis among all malignancies and is resistant to almost all current therapies. Attenuated Salmonella typhimurium strain VNP20009 has been deployed as powerful anticancer agent in a variety of animal cancer models, and previous phase 1 clinical trials have proven its safety profiles. However, thus far, little is known about its effect on PDAC. Here, we established CFPAC-1 cell lines expressing an mKate2 protein and thus emitting far-red fluorescence in the subsequent xenograft implant. VNP20009 strain was further engineered to carry a luciferase cDNA, which catalyzes the light-emitting reaction to allow the observation of salmonella distribution and accumulation within tumor with live imaging. Using such VNP20009 strain and intratumoral delivery, we could reduce the growth of pancreatic cancer by inducing apoptosis and severe necrosis in a dosage dependent manner. Consistent with this finding, intratumoral delivery of VNP20009 also increase caspase-3 activity and the expression of Bax protein. In summary, we revealed that VNP20009 is a promising bacterial agent for the treatment of PDAC, and that we have established a dual fluorescent imaging system as a valuable tool for noninvasive live imaging of solid tumor and engineered bacterial drug.
Micromechanics of deformation and stress evolution in thin films and patterned lines on substrates

In this thesis, we investigated the mechanical behavior of small volume structures, with specific application to thin metal films and patterned metal lines on substrates. The first part of this investigation dealt with the elastoplastic behavior of interconnect lines during thermal cycling. A robust computational method was developed to predict volume-averaged stresses in unpassivated and passivated lines in response to changes in temperature, as a function of line geometry, material properties and thermal history. The computational model also facilitated the extraction of substrate curvature. In addition, a simple analytical method was developed to allow extraction of volume-averaged stresses in unpassivated lines upon yielding due to thermal stresses, via experimental curvature methods. The second part of the investigation involved the systematic nanoindentation of a wide range of FCC single crystals and polycrystals, in bulk and thin film form. For shallow (≤ 100 nm) depths, the experimentally obtained P–h curves displayed elastic loading portions alternated with inelastic displacement bursts, for all specimens. The bursts were attributed to dislocation nucleation and motion within the crystal, which occurred when stresses underneath the indenter tip approached the critical shear strength of the material. Theories of dislocation activity were confirmed with planar TEM photos of nanoindented Cu films. In order to examine the atomistics of such phenomena, an experimental 2-D atomic simulation was developed, via an extension of the classical soap bubble raft, to simulate elastic contact and defect nucleation at low loads. Dislocation nucleation inside crystals of low defect density, ostensibly requiring stresses on the order of the theoretical shear strength, was found to occur under blunt indenters, providing a mechanistic justification for bursts observed during nanoindentation experiments. Finally, the experimental nanoindentation results for thin films were analyzed in the context of elastoplastic indentation, incorporating elastic loading and inelastic bursts. Stiffnesses thus obtained were found to increase as film thickness decreased, displaying a similar trend to literature thin film strength values obtained via substrate curvature methods. Thesis Supervisor: Subra Suresh Title: R.P. Simmons Professor of Materials Science and Engineering
PCNA directs type 2 RNase H activity on DNA replication and repair substrates

Ribonuclease H2 is the major nuclear enzyme degrading cellular RNA/DNA hybrids in eukaryotes and the sole nuclease known to be able to hydrolyze ribonucleotides misincorporated during genomic replication. Mutation in RNASEH2 causes Aicardi–Goutières syndrome, an auto-inflammatory disorder that may arise from nucleic acid byproducts generated during DNA replication. Here, we report the crystal structures of Archaeoglobus fulgidus RNase HII in complex with PCNA, and human PCNA bound to a C-terminal peptide of RNASEH2B. In the archaeal structure, three binding modes are observed as the enzyme rotates about a flexible hinge while anchored to PCNA by its PIP-box motif. PCNA binding promotes RNase HII activity in a hinge-dependent manner. It enhances both cleavage of ribonucleotides misincorporated in DNA duplexes, and the comprehensive hydrolysis of RNA primers formed during Okazaki fragment maturation. In addition, PCNA imposes strand specificity on enzyme function, and by localizing RNase H2 and not RNase H1 to nuclear replication foci in vivo it ensures that RNase H2 is the dominant RNase H activity during nuclear replication. Our findings provide insights into how type 2 RNase H activity is directed during genome replication and repair, and suggest a mechanism by which RNase H2 may suppress generation of immunostimulatory nucleic acids.
One-Bit Precoding and Constellation Range Design for Massive MIMO With QAM Signaling

The use of low-resolution digital-to-analog converters (DACs) for transmit precoding provides crucial energy efficiency advantage for massive multiple-input multiple-output (MIMO) implementation. This paper formulates a quadrature amplitude modulation (QAM) constellation range and a one-bit symbol-level precoding design problem for minimizing the average symbol error rate (SER) in downlink massive MIMO transmission. A tight upper bound for the SER with low-resolution DAC precoding is first derived. The derived expression suggests that the performance degradation of one-bit precoding can be interpreted as a decrease in the effective minimum distance of the QAM constellation. Using the obtained SER expression, we propose a QAM constellation range design for the single-user case. It is shown that in the massive MIMO limit, a reasonable choice for constellation range with one-bit precoding is that of the infinite-resolution precoding with per-symbol power constraint, but reduced by a factor of $\sqrt{2/\pi }$ or about 0.8. The corresponding minimum distance reduction translates to about a 2 dB gap between the performance of one-bit precoding and infinite-resolution precoding. This paper further proposes a low-complexity heuristic algorithm for the one-bit precoder design. Finally, the proposed QAM constellation range and precoder design are generalized to the multiuser downlink. We propose to scale the constellation range for the infinite-resolution zero-forcing (ZF) precoding with per-symbol power constraint by the same factor of $\sqrt{2/\pi }$ for one-bit precoding. The proposed one-bit precoding scheme is shown to be within 2 dB of infinite-resolution ZF. In term of number of antennas, one-bit precoding requires about 50% more antennas to achieve the same performance as infinite-resolution precoding.
Expression of a Testis-Specific Nuclear Protein, TRA98, in Mouse Testis during Spermatogenesis. A Quantitative and Qualitative Immunoelectron Microscopy (IEM) Analysis

TRA98 is a testis-specific nuclear protein, but its biological role is unclear. We analyzed the localization of TRA98 in developing spermatogenic cells using immunofluorescence (IF) and immunoelectron microscopy (IEM). TRA98 was localized exclusively to the nuclei. In spermatocytes, IF staining was associated with certain sub-nuclear structures to show a reticular pattern; the XY body was strongly stained. In spermatids, both reticular and punctate staining patterns were observed. In late spermatids, staining decreased as cell dif-ferentiation proceeded. However, epididymal sperm were strongly stained when smear preparations were not fixed, or followed by treatment with 4 M urea or 2% mercaptoethanol. IEM showed that gold signals were closely associated with electron-dense masses but not with the nucleoli. We then investigated the expression of TRA98 in differentiating spermatocytes using a quantitative IEM technique. A small expression peak was observed around stage II-III and a second large peak was noted at stage XI. In spermatids, a single expres-sion peak was observed at step 5; labeling density then decreased gradually but did not reach zero. In early spermatids, heterochromatin was stained much more than euchromatin. The results suggest that the function of TRA98 increases at three points during spermatogenesis. In addition, TRA98 is maintained in the sperm head and carried into the egg after fertilization.
Efficacy and safety of tanezumab in the treatment of pain from bone metastases

Abstract Patients with metastatic bone cancer report life-altering pain. Nerve growth factor is involved in pain signaling. Tanezumab, a nerve growth factor monoclonal antibody, has demonstrated efficacy in chronic pain. Placebo-controlled parent (NCT00545129; study 1003) and noncontrolled open-label extension (NCT00830180; study 1029) studies evaluated efficacy and safety of tanezumab in patients with painful bone metastases taking daily opioids. Patients in study 1003 received a single intravenous injection of 10 mg tanezumab or placebo and were followed up to 16 weeks. Efficacy analyses included change from baseline in daily average and worst pain at week 6 on an 11-point numeric rating scale. At week 8, patients could enroll in study 1029 and receive 4 infusions of 10 mg tanezumab at 8-week intervals with follow-up to 40 weeks. Safety assessments included adverse events and physical and neurologic examinations. Overall, 59 patients were randomized and treated (placebo, n = 30; tanezumab, n = 29). At the primary endpoint of study 1003, least squares mean (SE) difference in change from baseline in daily average pain vs placebo was −0.26 (0.45; P = 0.569). Post hoc analyses suggested that tanezumab had greater efficacy in patients with lower baseline opioid use and/or higher baseline pain. Mean (SE) pain scores in study 1029 were reduced through week 40 compared with study 1029 or 1003 baselines (−0.21 [0.76] and −1.27 [0.68], respectively). Adverse event incidence of study 1003 was similar between groups. Although the primary endpoint was not achieved, tanezumab may provide additional sustained analgesia in patients with metastatic bone pain taking daily opioids. Additional larger studies are warranted.
Mapping Images to Scene Graphs with Permutation-Invariant Structured Prediction

Structured prediction is concerned with predicting multiple inter-dependent labels simultaneously. Classical methods like CRF achieve this by maximizing a score function over the set of possible label assignments. Recent extensions use neural networks to either implement the score function or in maximization. The current paper takes an alternative approach, using a neural network to generate the structured output directly, without going through a score function. We take an axiomatic perspective to derive the desired properties and invariances of a such network to certain input permutations, presenting a structural characterization that is provably both necessary and sufficient. We then discuss graph-permutation invariant (GPI) architectures that satisfy this characterization and explain how they can be used for deep structured prediction. We evaluate our approach on the challenging problem of inferring a {\em scene graph} from an image, namely, predicting entities and their relations in the image. We obtain state-of-the-art results on the challenging Visual Genome benchmark, outperforming all recent approaches.
Stock Prices and Monetary Policy: Re-examining the Issue in a New Keynesian Model with Endogenous Investment

Abstract In this paper the authors present a New Keynesian quantitative model with endogenous investment and stock-market sector that may shed further light on two unsettled issues: whether central banks should include some financial indicator in their policy rules, and which indicator may be expected to generate better stabilization performance. For comparative purposes the authors replicate the policy framework and assessment strategy of the well-known ‘no-inclusion’ model of Bernanke–Gertler (Monetary Policy and Asset Price Volatility, 1999, and Should Central Banks Respond to Movements in Asset Prices? 2001). The performance of five policy rules is assessed. Two are ‘traditional’ Taylor rules (i.e. with no financial indicators) that differ in the relative weight on the output and inflation gaps. Three are ‘financial’ Taylor rules, that is, augmented with one financial indicator: the deviation from trend of stock prices, of Tobin’s q (the rate of change stock prices relative to capital stock) and of investment. The authors show results that are at variance with Bernanke–Gertler. First, because among the traditional rules the best performing one is output aggressive instead of inflation aggressive. Second, because the financial rule with Tobin’s q outperforms the traditional inflation-aggressive one under all dimensions and cases. However, the authors cannot draw a univocal conclusion as regards the comparison between the financial rule with Tobin’s q and the traditional but output aggressive rule.
Biological evaluations of commercial dicalcium phosphates as sources of available phosphorus for broiler chicks.

One thousand male Hubbard chicks were used in a 21-d study (10 birds per battery cage) to determine relative biological availability of phosphorus in seven samples of commercial dicalcium phosphate, expected to contain variable amounts of monocalcium phosphate. Five samples were from established producers in Brazil and two from the U.S. Pure calcium phosphate dibasic dihydrate was used as the reference standard. Phosphates were added to the corn-soybean basal diet (22.5% CP; 0.4% total phosphorus) to provide 0.1, 0.2, and 0.3% supplemental phosphorus. The calcium level was 1.0% for all diets. Left tibias were removed for bone ash (BA) and bone strength (BS) determination. Body weight, feed intake (FI), BA, BS, and plasma phosphorus increased (P < 0.01) and plasma calcium and alkaline phosphatase decreased (P < 0.01) with increasing dietary phosphorus regardless of source. The availability of phosphorus for each test phosphate was determined by slope ratio, with BW, BA, and BS regressed on phosphorus added within each phosphorus source. A relative biological value (RBV) was calculated based on BW, BA, and gain:feed ratio. Availability based on BW ranged from 97.07 to 110.41%. When BA was the criterion, values were 80.32 to 107.84% and for BS were 79.34 to 110.52%. The RBV ranged from 97.55 to 100.60%. Phosphate sources did not vary greatly in phosphorus availability. Overall phosphorus availability averages were higher for BW (103%) and RBV (99%) and lowest for BA (96%) and BS (94%).
Apixaban for the Secondary Prevention of Thrombosis Among Patients With Antiphospholipid Syndrome

Background: Antiphospholipid syndrome (APS) is an acquired thrombophilia characterized by thrombosis, pregnancy morbidity, and the presence of characteristic antibodies. Current therapy for patients having APS with a history of thrombosis necessitates anticoagulation with the vitamin K antagonist warfarin, a challenging drug to manage. Apixaban, approved for the treatment and prevention of venous thrombosis with a low rate of bleeding observed, has never been studied among patients with APS. Aims and Methods: We report study rationale and design of Apixaban for the Secondary Prevention of Thrombosis Among Patients With Antiphospholipid Syndrome (ASTRO-APS), a prospective randomized open-label blinded event pilot study that will randomize patients with a clinical diagnosis of APS receiving therapeutic anticoagulation to either adjusted-dose warfarin or apixaban 2.5 mg twice a day. We aim to report our ability to identify, recruit, randomize, and retain patients with APS randomized to apixaban compared with warfarin. We will report clinically important outcomes of thrombosis and bleeding. All clinical outcomes will be adjudicated by a panel blinded to the treatment arm. A unique aspect of this study is the enrollment of patients with an established clinical diagnosis of APS. Also unique is our use of electronic medical record interrogation techniques to identify patients who would likely meet our inclusion criteria and use of an electronic portal for follow-up visit data capture. Conclusion: ASTRO-APS will be the largest prospective study to date comparing a direct oral anticoagulant with warfarin among patients with APS for the secondary prevention of thrombosis. Our inclusion criteria assure that outcomes obtained will be clinically applicable to the routine management of patients with APS receiving indefinite anticoagulation.
Electromyographic Activity of Lower Body Muscles during the Deadlift and Still-Legged Deadlift

Bezerra ES, Simão, R, Fleck SJ, Paz G, Maia M, Costa PB, Amadio AC, Miranda H, Serrão JC. Electromyographic Activity of Lower Body Muscles during the Deadlift and Still-Legged Deadlift. JEPonline 2013;16(3):30-39. The purpose of this study was to analyze eletromyographic (EMG) signal of biceps femoris (BF), vastus lateralis (VL), lumbar multifidus (LM), anterior tibialis (AT), and medial gastrocnemius (MG) during the deadlift (DL) and stiff-legged deadlift (SLDL). Fourteen men (26.71 ± 4.99 yrs; body mass 88.42 ± 12.39 kg; 177.71 ± 8.86 cm) voluntarily participated in this study. The data were obtained on three non-consecutive days separated by 48 hrs. In the first day, anthropometric measures and the repetition maximum testing (1 RM) for both exercises were applied in a counter-balanced cross-over design. On the second day, the 1 RM was re-tested. On the third day, both exercises were performed at 70% of 1 RM and the EMG data were collected. Parameters related to the RMS during the movement, temporal activation patterns, and relative times of activation were analyzed for each muscle. The maximum activation level for VL during the DL (128.3 ± 33.9% of the EMG peak average) was significantly different (P = 0.027) from the SLDL (101.1 ± 14% of the EMG peak average). These findings should be useful when emphasizing different muscle groups in a resistance training program
A MIMO H-shape Dielectric Resonator Antenna for 4G Applications

In this article, a Multiple-Input-Multiple-Output (MIMO) H-shape Dielectric Resonator Antenna (DRA) is designed and simulated at 2.6 GHz for 4G applications. The proposed structure consists of H-shape DRA ( =10) which is mounted on FR4 substrate ( =4.6), and feed by two different feeding mechanisms. First, microstrip with slot coupling as Port 1. Second, coaxial probe as Port 2. The electrical properties of the proposed MIMO H-shape DRA in term of return loss, bandwidth and gain are completely obtained by using CST Microwave Studio Suite Software. The simulated results demonstrated a return loss more than 20 dB, an impedance bandwidth of 26 % (2.2 – 2.9 GHz), and gain of 6.11 dBi at Port 1. Then, a return loss more than 20 dB, an impedance bandwidth of 13 % (2.2 – 2.7 GHz), and gain of 6.63 dBi at Port 2. Both ports indicated impedance bandwidth more than 10 %, return loss lower than 20 dB, and gain more than 10 dBi at 2.6 GHz. The simulated electrical properties of the proposed design show a good potential for LTE applications.
The Effects of the January 2016 UTC Offset Anomaly on GPS-Controlled Clocks Monitored at NIST

Errors in the Coordinated Universal Time (UTC) offset parameters broadcast by Global Positioning System (GPS) satellites caused many thousands of GPS-controlled clocks to be in error by approximately -13 μs on January 25-26, 2016. The erroneous UTC offset information was broadcast by 15 GPS satellites, or half of the available constellation, during the anomaly. This paper discusses the technical reasons for the UTC offset anomaly, its effect on clocks controlled by GPS satellites (hereafter referred to as GPS clocks), and how it was detected at the National Institute of Standards and Technology (NIST). It then discusses the impact of the UTC offset anomaly on GPS clocks maintained and monitored by NIST, including clocks located in Boulder, Colorado and those at remote locations. Some analysis is presented of the effects of the UTC offset anomaly on GPS clocks located at 19 sites in North, Central, and South America.
Inferring Strain Mixture within Clinical Plasmodium falciparum Isolates from Genomic Sequence Data

We present a rigorous statistical model that infers the structure of P. falciparum mixtures—including the number of strains present, their proportion within the samples, and the amount of unexplained mixture—using whole genome sequence (WGS) data. Applied to simulation data, artificial laboratory mixtures, and field samples, the model provides reasonable inference with as few as 10 reads or 50 SNPs and works efficiently even with much larger data sets. Source code and example data for the model are provided in an open source fashion. We discuss the possible uses of this model as a window into within-host selection for clinical and epidemiological studies.