Miracle-dz/UniFAR-FTUs huggingface dataset:
C-5-Modified Tetrahydropyrano-Tetrahydofuran-Derived Protease Inhibitors (PIs) Exert Potent Inhibition of the Replication of HIV-1 Variants Highly Resistant to Various PIs, including Darunavir

ABSTRACT We identified three nonpeptidic HIV-1 protease inhibitors (PIs), GRL-015, -085, and -097, containing tetrahydropyrano-tetrahydrofuran (Tp-THF) with a C-5 hydroxyl. The three compounds were potent against a wild-type laboratory HIV-1 strain (HIV-1WT), with 50% effective concentrations (EC50s) of 3.0 to 49 nM, and exhibited minimal cytotoxicity, with 50% cytotoxic concentrations (CC50) for GRL-015, -085, and -097 of 80, >100, and >100 μM, respectively. All the three compounds potently inhibited the replication of highly PI-resistant HIV-1 variants selected with each of the currently available PIs and recombinant clinical HIV-1 isolates obtained from patients harboring multidrug-resistant HIV-1 variants (HIVMDR). Importantly, darunavir (DRV) was >1,000 times less active against a highly DRV-resistant HIV-1 variant (HIV-1DRVR P51); the three compounds remained active against HIV-1DRVR P51 with only a 6.8- to 68-fold reduction. Moreover, the emergence of HIV-1 variants resistant to the three compounds was considerably delayed compared to the case of DRV. In particular, HIV-1 variants resistant to GRL-085 and -097 did not emerge even when two different highly DRV-resistant HIV-1 variants were used as a starting population. In the structural analyses, Tp-THF of GRL-015, -085, and -097 showed strong hydrogen bond interactions with the backbone atoms of active-site amino acid residues (Asp29 and Asp30) of HIV-1 protease. A strong hydrogen bonding formation between the hydroxyl moiety of Tp-THF and a carbonyl oxygen atom of Gly48 was newly identified. The present findings indicate that the three compounds warrant further study as possible therapeutic agents for treating individuals harboring wild-type HIV and/or HIVMDR. IMPORTANCE Darunavir (DRV) inhibits the replication of most existing multidrug-resistant HIV-1 strains and has a high genetic barrier. However, the emergence of highly DRV-resistant HIV-1 strains (HIVDRVR ) has recently been observed in vivo and in vitro. Here, we identified three novel HIV-1 protease inhibitors (PIs) containing a tetrahydropyrano-tetrahydrofuran (Tp-THF) moiety with a C-5 hydroxyl (GRL-015, -085, and -097) which potently suppress the replication of HIVDRVR . Moreover, the emergence of HIV-1 strains resistant to the three compounds was considerably delayed compared to the case of DRV. The C-5 hydroxyl formed a strong hydrogen bonding interaction with the carbonyl oxygen atom of Gly48 of protease as examined in the structural analyses. Interestingly, a compound with Tp-THF lacking the hydroxyl moiety substantially decreased activity against HIVDRVR . The three novel compounds should be further developed as potential drugs for treating individuals harboring wild-type and multi-PI-resistant HIV variants as well as HIVDRVR .
Nonpathogenic Strains of Colletotrichum lindemuthianum Trigger Progressive Bean Defense Responses during Appressorium-Mediated Penetration

ABSTRACT The fungal bean pathogen Colletotrichum lindemuthianum differentiates appressoria in order to penetrate bean tissues. We showed that appressorium development in C. lindemuthianum can be divided into three stages, and we obtained three nonpathogenic strains, including one strain blocked at each developmental stage. H18 was blocked at the appressorium differentiation stage; i.e., no genuine appressoria were formed. H191 was blocked at the appressorium maturation stage; i.e., appressoria exhibited a pigmentation defect and developed only partial internal turgor pressure. H290 was impaired in appressorium function; i.e., appressoria failed to penetrate into bean tissues. Furthermore, these strains could be further discriminated according to the bean defense responses that they induced. Surprisingly, appressorium maturation, but not appressorium function, was sufficient to induce most plant defense responses tested (superoxide ion production and strong induction of pathogenesis-related proteins). However, appressorium function (i.e., entry into the first host cell) was necessary for avirulence-mediated recognition of the fungus.
A Johnson-type bound for group codes and lattices

In this work we give and analyze a Johnson-type bound for group codes considering the G-norm. Johnson bounds have been given for binary and q-ary codes [5, 7, 8] with respect to the Hamming distance. We borrow the idea of the G-norm from [3] and define a new distance for codewords: the G-semidistance. We extend the Johnson-type bounds for binary and q-ary codes to the Gsemidistance and give a relation between these bounds and our G-semidistance. By means of this, we present an upper bound on the number of codewords inside a G-ball and an l1-ball, within a certain given radius, for both group codes and lattices. Johnson-type bounds provide an upper bound on the number of codewords in a Hamming ball with a specified radius. The original proof is based on linear algebra [5, 8]; proofs with a geometric view are presented in [1]. The extension of Johnson-type bounds for q-ary codes is given in [7]. In all of these works the Johnson-type bounds use Hamming balls. Here we consider G-balls with an arbitrary received vector as the G-ball’s center, given a specified radius; we find an upper bound for the number of codewords in the G-ball. Roughly speaking, we investigate the number of codewords such that their G-semidistances from the received word is less than the radius of the G-ball. Recently the question of list decoding under the Hamming metric has become an important trend in coding theory. In addition, list decoding for lattices are given in [6, 9]. Our Johnson-type bound, when applied to some recent works [2, 3], may lead to list decoding of q-ary codes, group codes and lattices via the G-norm. Let x = (x1, . . . , xn) be in a group code G. The G-norm for x is defined as ‖x‖G = x1 + x2 + · · ·+ xn where the operations are performed in R [3].
Rate-compatible punctured low-density parity-check codes for ultra wide band systems

In this paper we treat rate-compatible punctured low-density parity-check (RCP-LDPC) codes. We show how a mother code can be efficiently punctured to achieve good performance over a wide range of rates and discuss the design of a mother code. While this approach can be applied to virtually any time-varying channel, we apply it to the ultra wide band (UWB) channel, e.g. 802.15. 3a, and we show that RCP-LDPC codes perform well as compared to a selection of fixed rate unpunctured codes. They reduce the implementation complexity and enable the use of retransmission protocols based on incremental redundancy to increase the throughput
Clustering gene expression data using probabilistic non-negative matrix factorization

Non-negative matrix factorization (NMF) has proven to be a useful decomposition for multivariate data. Specifically, NMF appears to have advantages over other clustering methods, such as hierarchical clustering, for identification of distinct molecular patterns in gene expression profiles. The NMF algorithm, however, is deterministic. In particular, it does not take into account the noisy nature of the measured genomic signals. In this paper, we extend the NMF algorithm to the probabilistic case, where the data is viewed as a stochastic process. We show that the probabilistic NMF can be viewed as a weighted regularized matrix factorization problem, and derive the corresponding update rules. Our simulation results show that the probabilistic non-negative matrix factorization (PNMF) algorithm is more accurate and more robust than its deterministic homologue in clustering cancer subtypes in a leukemia microarray dataset.
Families in Bangladesh

This article on families in Bangladesh is a abridged version of an article published in UNESCOs "The Changing Family in Asia" in 1992. The author concludes that further research is needed at the micro-level multiregionally on changing life styles on the impact of increased nucleation on the social structure on the impact on family life from womens greater involvement in agricultural and manual labor pursuits and on the disintegration of families due to migration. A descriptive summary is given of the basic social organization of families including the "gusthi" (all male patrilineal descendants of a great-grandfather) and the "samaj" (people grouped on the basis of kinship and territory and with a socio-political identity). Families follow the patterns of joint extended and nuclear. Joint families include three or more generations living together. Extended families are a group of nuclear families and related individuals from several generations living together. In 1972 the number of nuclear families was reported to be about 51-58% in villages. Population growth in Bangladesh did not result in an increased number of households only in increased household size. Higher average size of households predominated in Buddhist households followed by Muslim and Hindu households. Household size has been gradually increasing in Chittagong Khulna and Rajshahi while fertility has been declining. This pattern is attributed to a decrease in single member households a decrease in mortality and more extended families. Bangladesh had an excess male population during 1901-74. The sex ratio in rural areas has not changed over the decades before 1974. Mean age at marriage is increasing in urban and rural areas but at a faster rate in urban areas. 48% of total population are women and 90% live in rural areas. Male dominance continues to be reinforced by the kinship system. The practice of purdah keeps women isolated from society. The causes of family changes are not well researched in Bangladesh.
Natural History of Very Severe Aortic Stenosis

Background— We sought to assess the outcome of asymptomatic patients with very severe aortic stenosis. Methods and Results— We prospectively followed 116 consecutive asymptomatic patients (57 women; age, 67±16 years) with very severe isolated aortic stenosis defined by a peak aortic jet velocity (AV-Vel) ≥5.0 m/s (average AV-Vel, 5.37±0.35 m/s; valve area, 0.63±0.12 cm2). During a median follow-up of 41 months (interquartile range, 26 to 63 months), 96 events occurred (indication for aortic valve replacement, 90; cardiac deaths, 6). Event-free survival was 64%, 36%, 25%, 12%, and 3% at 1, 2, 3, 4, and 6 years, respectively. AV-Vel but not aortic valve area was shown to independently affect event-free survival. Patients with an AV-Vel ≥5.5 m/s had an event-free survival of 44%, 25%, 11%, and 4% at 1, 2, 3, and 4 years, respectively, compared with 76%, 43%, 33%, and 17% for patients with an AV-Vel between 5.0 and 5.5 m/s (P<0.0001). Six cardiac deaths occurred in previously asymptomatic patients (sudden death, 1; congestive heart failure, 4; myocardial infarction, 1). Patients with an initial AV-Vel ≥5.5 m/s had a higher likelihood (52%) of severe symptom onset (New York Heart Association or Canadian Cardiovascular Society class >II) than those with an AV-Vel between 5.0 and 5.5 m/s (27%; P=0.03). Conclusions— Despite being asymptomatic, patients with very severe aortic stenosis have a poor prognosis with a high event rate and a risk of rapid functional deterioration. Early elective valve replacement surgery should therefore be considered in these patients.
A Systemic Review of Obstructive Sleep Apnea and Its Implications for Anesthesiologists

BACKGROUND: Obstructive sleep apnea (OSA) is present in a significant proportion of the population, but the majority of patients remain undiagnosed. It is crucial that anesthesiologists and surgeons recognize the increased perioperative risks associated with undiagnosed OSA. We present a systematic review of the literature on the perioperative management of surgical patients with OSA. METHODS: The scope of this review is restricted to publications in all surgical specialties and in the adult patient population. The main search key words were: “perioperative care,” “sleep apnea,” “obstructive sleep apnea,” “perioperative risk,” and “perioperative care. ” The databases Medline, Embase, Biological Abstract, Science Citation Index, and Healthstar were searched for relevant English language articles from 1966 to March 2007. RESULTS: The literature supports an increased perioperative risk in OSA patients. The American Society of Anesthesiologists guidelines support the routine screening for OSA during preoperative assessment, and methods of OSA screening are discussed in this review. This review suggests a number of perioperative management strategies to reduce surgical risk in patients with OSA. However, apart from the consensus-based American Society of Anesthesiologists guidelines, it is important to note that evidence-based recommendations are lacking in the literature. CONCLUSIONS: This review suggests ways to screen for OSA in the preoperative setting and proposes perioperative management strategies. The ultimate goal is to reduce the perioperative risk of OSA patients but, to realize that goal, research will be needed to determine whether screening for OSA and/or adapting specific perioperative management approaches translates into a lessening of adverse events in surgical patients with undiagnosed OSA.
Design of a bladder based elastomeric Smart Shoe for haptic terrain display

Haptic terrain display in Virtual Environments is important for increasing realism and immersion. While several terrain display devices exist, the Smart Shoe aims to render subtle terrain features while still being able to accommodate gross features, like sloped terrain. The compactness and portability of this haptic wearable device allows it to not only display terrain features on flat treadmill surface, but also potentially be able to compensate terrain unevenness to maintain level ankle posture for rehabilitation purposes. A novel elastomer based bladder system is designed to provide elasticity and support of the Smart Shoe. A mechatronic top plate is made by molding electronics and miniature solenoid valves into rubber material, providing sensing and control of pressure and height of the shoe. Evaluations of the Smart Shoe indicate promises to improve the haptic perception of different terrain features in a virtual environment.
List-Decoding Multiplicity Codes

We study the list-decodability of multiplicity codes. These codes, which are based on evaluations of high-degree polynomials and their derivatives, have rate approaching 1 while simultaneously allowing for sublinear-time error correction. In this paper, we show that multiplicity codes also admit powerful list-decoding and local list-decoding algorithms that work even in the presence of a large error fraction. In other words, we give algorithms for recovering a polynomial given several evaluations of it and its derivatives, where possibly many of the given evaluations are incorrect. Our first main result shows that univariate multiplicity codes over fields of prime order can be list-decoded up to the so-called "list-decoding capacity. " Specifically, we show that univariate multiplicity codes of rate R over fields of prime order can be list-decoded from a (1 R e) fraction of errors in polynomial time (for constant R;e). This resembles the behavior of the "Folded Reed-Solomon Codes" of Guruswami and Rudra (Trans. Info. Theory 2008). The list-decoding algorithm is based on constructing a differential equation of which the desired codeword is a solution; this differential equation is then solved using a power-series approach (a variation of Hensel lifting) along with other algebraic ideas. Our second main result is a list-decoding algorithm for decoding multivariate multiplicity codes up to their Johnson radius. The key ingredient of this algorithm is the construction of a special family of "algebraically-repelling" curves passing through the points of F m ; no moderate-degree multivariate polynomial over F m can simultaneously vanish on all these A version of this paper was posted online as an Electronic Colloq. on Computational Complexity Tech. Report (20). Supported in part by a Sloan Fellowship and NSF grant CCF-1253886.
Lactic dehydrogenase isoenzyme electrophoretic patterns in the diagnosis of pleural effusion

The relative value of each lactic dehydrogenase isoenzyme (iso LDH) was measured by electrophoretic separation in the serum and the pleural fluid of 100 patients. In each case, the cause of the pleural effusion was known. Two types of LDH isoenzyme pattern were found in the serum: a normal type with a low value of LDH 5 and an abnormal type with a high value of LDH 5. This high LDH‐5 level is due to an impaired liver function. In the pleural fluid, the electrophoretic patterns of five LDH isoenzymes were found by computerized processing. During congestive heart failure (28 cases) the electrophoretic pattern of the LDH isoenzymes was always similar in the serum and in the pleural fluid (transudative pleural effusion). During thoracic empyema, the relative values of the isoenzymes in the pleural fluid were regularly increasing from LDH 1 to LDH 5. In this situation, the evaluation of LDH 5 appeared to emanate from the increased granulocytes in the pleural fluid. In 22 inflammatory pleural effusions, the relative values of the five isoenzymes were equal. During malignant effusions (35 cases) a high level of LDH 5 was found in 21 patients. LDH 5 is known to be secreted by malignant tissue, and the authors confirmed it by finding a high level of LDH 5 in biopsy specimens of patients with mesothelioma or epidermoid lung cancer (7 cases). Conversely, the level of LDH 5 was low in biopsy specimens from normal lung tissue or benign inflammatory pleuritis (6 cases). Among the 14 patients with low levels of LDH 5 in the pleural fluid during malignant pleural effusion, the authors found the malignant lymphomas (three cases) and the small cell lung carcinoma (five cases). In these cases, the low level of LDH 5 was in agreement with the result of a low level of LDH 5 found in the biopsy of a metastatic liver localization of a small cell lung carcinoma. So the electrophoretic determination of LDH isoenzymes pattern in pleural fluid is a sensitive tool for the management of pleural effusion.
A unique calorimeter-cycler for evaluating high-power battery modules

Battery thermal management is critical for high-power battery packs commonly used in electric vehicles (EV) and hybrid electric vehicles (HEV). To design battery thermal management systems properly, obtaining accurate heat generation data from battery modules is essential. To measure heat generation from full-size multiple-cell battery modules, we developed and tested a custom-made calorimeter for large modules. Battery modules with dimensions up to 21 cm/spl times/39 cm in cross section and 20 cm in height can be placed in the cavity of the calorimeter for measuring heat generation rates from 1 W to 100 W with the battery operating at -30/spl deg/C to +60/spl deg/C. The instrument is capable of measuring heat effects as small as 10 joules with accuracy of 5%. A state-of-the-art high power battery cycler is used to cycle the modules in the calorimeter. This paper provides a description of the calorimeter, calibration test results on its performance, and test results from a module simulating a HEV lead-acid battery.
Brain targeting of Atorvastatin loaded amphiphilic PLGA-b-PEG nanoparticles

The objective of this study was to develop polysorbate 80 coated and Atorvastatin loaded poly(lactic-co-glycolic acid)-block-poly(ethylene glycol) (PLGA-b-PEG) nanoparticles and to investigate advantages of coating on nanoparticles for brain delivery of Atorvastatin. The nanoparticles were prepared by nanoprecipitation method. The effects of polymer concentration, PEG content and polysorbate 80 coating on the particle size, drug loading efficiency and release behaviour of nanoparticles were investigated. Additionally, cellular uptake and brain targeting of formulated nanoparticles were studied. Particle sizes were in the range of 30–172 nm depending on formulation parameters. Increasing the polymer concentration significantly increased the nanoparticle size. Decreasing the PEG content from 15% to 5% (w/w) in polymer composition increased the nanoparticle size from 69 to 172 nm. Both coated and uncoated polysorbate 80 nanoparticles were effectively internalised within the endothelial cells. Moreover, both types of nanoparticles were able to penetrate the blood brain barrier and reach the maximum in brain 1 h post injection. It was concluded that these nanoparticles are promising nanosystems for treatment of neurological disorders.
To grow old: regulatory role of ethylene and jasmonic acid in senescence

Senescence, the final stage in the development of an organ or whole plant, is a genetically programmed process controlled by developmental and environmental signals. Age-related signals underlie the onset of senescence in specific organs (leaf, flower, and fruit) as well as the whole plant (monocarpic senescence). Rudimentary to most senescence processes is the plant hormone ethylene, a small gaseous molecule critical to diverse processes throughout the life of the plant. The role of ethylene in senescence was discovered almost 100 years ago, but the molecular mechanisms by which ethylene regulates senescence have been deciphered more recently primarily through genetic and molecular studies in Arabidopsis. Jasmonic acid (JA), another plant hormone, is emerging as a key player in the control of senescence. The regulatory network of ethylene and JA involves the integration of transcription factors, microRNAs, and other hormones. In this review, we summarize the current understanding of ethylene’s role in senescence, and discuss the interplay of ethylene with JA in the regulation of senescence.
Cell shape and interaction defects in alpha-spectrin mutants of Drosophila melanogaster

We show that the alpha-spectrin gene is essential for larval survival and development by characterizing several alpha-spectrin mutations in Drosophila. P-element minigene rescue and sequence analysis were used to identify the alpha-spectrin gene as the l(3)dre3 complementation group of the Dras-Roughened-ecdysoneless region of chromosome 3 (Sliter et al., 1988). Germ line transformants carrying an alpha-spectrin cDNA, whose expression is driven by the ubiquitin promoter, fully rescued the first to second instar lethality characteristic of the l(3)dre3 alleles. The molecular defects in two gamma-ray-induced alleles were identified. One of these mutations, which resulted in second instar lethality, contained a 73-bp deletion in alpha-spectrin segment 22 (starting at amino acid residue 2312), producing a premature stop codon between the two EF hands found in this segment. The second mutation, which resulted in first instar lethality, contained a 20 base pair deletion in the middle of segment 1 (at amino acid residue 92), resulting in a premature stop codon. Examination of the spectrin- deficient larvae revealed a loss of contact between epithelial cells of the gut and disruption of cell-substratum interactions. The most pronounced morphological change was seen in tissues of complex cellular architecture such as the middle midgut where a loss of cell contact between cup-shaped cuprophilic cells and neighboring interstitial cells was accompanied by disorganization of the cuprophilic cell brush borders. Our examination of spectrin deficient larvae suggests that an important role of non-erythroid spectrin is to stabilize cell to cell interactions that are critical for the maintenance of cell shape and subcellular organization within tissues.