cssi/SciSciGPT-SciSciNet huggingface dataset:
Supporting fault-tolerance in streaming grid applications

This paper considers the problem of supporting and efficiently implementing fault-tolerance for tightly-coupled and pipelined applications, especially streaming applications, in a grid environment. We provide an alternative to basic checkpointing and use the notion of light-weight summary structure(LSS) to enable efficient failure-recovery. The idea behind LSS is that at certain points during the execution of a processing stage, the state of the program can be summarized by a small amount of memory. This allows us to store copies of LSS for enabling failure-recovery, which causes low overhead fault-tolerance. Our work can be viewed as an optimization and adaptation of the idea of application-level checkpointing to a different execution environment, and for a different class of applications. Our implementation and evaluation of LSS based failure- recovery has been in the context of the GATES (grid-based adaptive execution on streams) middleware. An observation we use for providing very low overhead support for fault-tolerance is that algorithms analyzing data streams are only allowed to take a single pass over data, which means they only perform approximate processing. Therefore, we believe that in supporting fault-tolerant execution for these applications, it is acceptable to not analyze a small number of packets of data during failure-recovery. We show how we perform failure-recovery and also demonstrate how we could use additional buffers to limit data loss during the recovery procedure. We also present an efficient algorithm for allocating a new computation resource for failure-recovery at runtime. We have extensively evaluated our implementation using three stream data processing applications, and shown that the use of LSS allows effective and low-overhead failure-recovery.
COLLABORATION STRUCTURE AND PERFORMANCE IN NEW SOFTWARE DEVELOPMENT: FINDINGS FROM THE STUDY OF OPEN SOURCE PROJECTS

The state of software development performance is far from being exemplar, with a success rate well below that of other industries, and understanding how to improve these projects is not only substantive but urgent. Software development is at most times a collaborative effort, yet we do not understand clearly how different collaboration structures associate with development performance metrics. This paper empirically examines the association between collaboration patterns, project productivity and product quality through a field study of working software open source new product development teams, using archival data from electronic sources related to Open Source Software projects. Collaboration structures are measured using Social Network Analysis and in terms of their network density, network centralization and the level of boundary spanning activity of team members. Productivity and quality are measured using "hard", code-based metrics. Results of regression analyses testing relevant hypotheses suggest that project managers need to strongly encourage internal collaboration, but be wary of allowing team members to participate in multiple projects. The breadth of skills within the team is a tactical asset that may increase the efficient frontier in the quality–productivity trade-off. Results also show that centralized structures associate with higher product quality and development productivity.
Recoverable distributed shared virtual memory: memory coherence and storage structures

An examination is made of the problem of implementing rollback recovery in multicomputer distributed shared virtual memory environments, in which the shared memory is implemented in software and exists only virtually. A user-transparent checkpointing recovery scheme and a twin-page disk storage management are presented to implement a recoverable distributed shared virtual memory. The checkpointing scheme is integrated with the shared virtual memory management. The twin-page disk approach allows incremental checkpointing without an explicit 'undo' at the time of recovery. A single consistent checkpoint state is maintained on stable disk storage. The recoverable distributed shared virtual memory allows the system to restart computation from a previous checkpoint after a processor failure without a global restart. >
A molten globule intermediate of the Von Willebrand factor A1 domain firmly tethers platelets under shear flow

Clinical mutations in patients diagnosed with Type 2A von Willebrand disease (VWD) have been identified that break the single disulfide bond linking N- and C-termini in the vWF A1 domain. We have modeled the effect of these mutations on the disulfide-bonded structure of A1 by reducing and carboxy-amidating these cysteines. Solution biophysical studies show that loss of this disulfide bond induces a molten globule conformational state lacking global tertiary structure but retaining residual secondary structure. The conformational dependence of platelet adhesion to these native and molten globule states of A1 is quantitatively compared using real-time high-speed video microscopy analysis of platelet translocation dynamics under shear flow in a parallel plate microfluidic flow chamber. While normal platelets translocating on surface-captured native A1 domain retain the catch-bond character of pause times that increase as a function of shear rate at low shear and decrease as a function of shear rate at high shear, platelets that interact with A1 lacking the disulfide bond remain stably attached and do not translocate. Based on these findings, we propose that the shear stress-sensitive regulation of the A1-GPIb interaction is due to folding the tertiary structure of this domain. Removal of the tertiary structure by disrupting the disulfide bond destroys this regulatory mechanism resulting in high-strength interactions between platelets and vWF A1 that are dependent only on residual secondary structure elements present in the molten globule conformation.
A local dependence measure and its application to screening for high correlations in large data sets

Correlation screening is frequently the only practical way to discover dependencies in very high dimensional data. In correlation screening a high threshold is applied to the matrix of sample correlation coefficients of the multivariate data. The variables having coefficients that exceed the threshold are called discoveries and are classified to be dependent. The mean number of discoveries and the number of false discoveries in correlation screening problems depend on a information-theoretic measure J, a novel type of information divergence that is a function of the joint density of pairs of variables. It is therefore important to estimate J in order to determine screening thresholds for desired false alarm rates. In this paper, we propose a kernel estimator for J, establish asymptotic consistency and determine the asymptotic distribution of the estimator. These results are used to minimize the MSE of the estimator and to determine confidence intervals on J. We use these results to test for dependence between variables in both simulated data sets and also between email spam harvesters. Finally, we use the estimate of J to determine screening thresholds in correlation screening problems involving gene expression data.
A Method to Evaluate the Biosynthesis of Glycosaminoglycans by the Aorta of Cynomolgus Monkey

Abstract The biosynthesis of the glycosaminoglycans (GAGs) was investigated in vitro in the aortic tissue of the Cynomolgus monkey incubated with [ 14 C]glucosamine. With the use of a new micromethod, it was possible to quantify the glycosaminoglycans and their radioactive distribution in the aortic tissue and incubation medium. Labeled and nonlabeled chondroitin 6-sulfate, dermatan sulfate, heparan sulfate and hyaluronic acid were measured. Since the sensitivity of this procedure is between 5 and 20 μg of GAGs, as little as 5 mg of dry defatted aortic tissue is sufficient for chemical and radioactive analyses.
Global Software Servicing: Observational Experiences at Microsoft

Software servicing in an important software engineering activity that is gaining significant importance in the global software development context. In this paper we report on a study conducted to understand the processes, practices and problems in the Windows servicing organization in Microsoftpsilas India Development Center. We report on our observations and experiences from this study on the main processes and practices adopted for software servicing in Windows and the main problems pertaining to information needs and communication issues. We also discuss our experiences in this study within the context of prior research defined in the global software development community to explain the ways in which Microsoft addresses these common problems.
On reordering instruction streams for pipelined computers

This paper describes a method to reorder the straight line instruction streams for pipelined computers which have one instruction issue unit but may contain multiple function units. The objective is to make the most efficient usage of the pipelines within the computer system. The input to the scheduler is the intermediate code of a compiler, and is represented by a data dependence graph (DDG).The scheduler is a kind of list scheduler. The data dependence and the pipeline effect of the function units within the system have been considered for finding a most suitable time slot for each node during reordering time.The scheduler has been implemented and several scientific application programs have been tested. The results show that in most of the cases the scheduler will achieve the optimal result. The average instruction issue rate is over 96%. As a comparison, the issue rate of an ordinary compiler is only 22%; and the issue rate of a compiler with the effect of pipeline but without reordering the instruction stream is about 45%.
Benefits of sulfamethoxazole-trimethoprim prophylaxis on rates of sepsis after kidney transplant.

Background The use of potent immunosuppression increases the risk of infectious complications following kidney transplantation. Sulfamethoxazole-trimethoprim (SMX/TMP) is an inexpensive broad-spectrum antimicrobial agent used in our center as lifelong prophylaxis against Pneumocystis jirovecii, unless contraindicated. This study evaluated the clinical impact of SMX/TMP prophylaxis compared with no prophylaxis with SMX/TMP (NoPPx), but with alternative agents. Methods This was a retrospective cohort analysis of renal transplant recipients (RTR) transplanted from January 2002 through December 2010. Patients were divided into SMX/TMP group and NoPPX group, based on whether they received prophylaxis with SMX/TMP or not, and rates of sepsis were compared between groups. We also analyzed the pathogens and source implicated in these episodes, as well as the dose of SMX/TMP. Rates were compared using multivariate logistic regression. Results With a mean follow-up of 4.8 (± 2.5) years, 63 cases of sepsis occurred in 1224 patients (5.1%), and 60% of these cases had a urinary source. The risk of sepsis was significantly reduced with prophylaxis vs. NoPPx (13.3% vs. 4.3% for SMX/TMP, P < 0.001), and this association was maintained through multivariate regression. Sepsis was associated with a numerically increased risk of graft loss and death that was not significantly affected by use of SMX/TMP. Conclusions Prophylaxis with SMX/TMP is an inexpensive way to reduce the incidence of sepsis in RTR.
Plasma α-l-Fucosidase Activity and the Risk of Borderline Epithelial Ovarian Tumors

The authors obtained venous blood samples from 106 female residents of western Washington in whom serous and mucinous borderline ovarian tumors had been diagnosed between 1980 and 1985 ("cases") and from a randomly selected telephone sample of 134 control women from the same counties. Mean activity in plasma of alpha-L-fucosidase was slightly higher in cases (334 units/ml) compared to controls (306 units/ml). The risk for a serous borderline tumor was virtually the same for women in all four quartiles of alpha-L-fucosidase activity. Women in the three lowest quartiles of activity were at 50-70% the risk of women in the highest quartile for the development of a mucinous tumor, but within these three quartiles there was no trend of decreasing risk with decreasing activity. These results suggest that for most women plasma alpha-L-fucosidase activity has little or no bearing on the risk of borderline ovarian tumors. Whether such an association exists in women genetically predisposed to these tumors could not be assessed.
Sticky Anaphase Aberrations after G2-Phase Arrest of Gamma-Irradiated Human Skin Fibroblasts: TP53 Independence of Formation and TP53 Dependence of Consequences

Abstract Redpath, J. L., Bengtsson, U., DeSimone, J., Lao, X., Wang, X. and Stanbridge, E. J. Sticky Anaphase Aberrations after G2-Phase Arrest of Gamma-Irradiated Human Skin Fibroblasts: TP53 Independence of Formation and TP53 Dependence of Consequences. Radiat. Res. 159, 57–71 (2003). We have studied the impact of TP53 status on the extent and nature of chromosome damage seen in human skin fibroblasts after γ irradiation beyond the G1-phase checkpoint but prior to the G2-phase checkpoint. Mitotic cells were examined in the absence and presence of treatment with nocodazole and the yield of aberrations was scored as a function of time postirradiation. The results revealed substantially greater damage in the absence of nocodazole, indicating that damage was being masked in its presence. While metaphase aberrations were seen exclusively in the presence of nocodazole, anaphase aberrations were seen principally in its absence. Furthermore, these were mostly of an unseparated, or “sticky”, type that showed sep...
Hodgkin's Disease and Anaplastic Large Cell Lymphoma Revisited. 1. unique cytokine and cytokine receptor profile distinguished from that of non-hodgkin's lymphomas.

In cultures, and in tissues as well, Hodgkin's and Reed-Sternberg (H-RS) cells and anaplastic large cell lymphoma (ALCL) cells are known to express a variety of cytokines, including IL-1, -5, -6, -8, -9, TNF-α, GM-CSF, M-CSF, TGF-β, CD70, CD80, and CD86. Various numbers of H-RS/ALCL cells may express cytokine receptors (R), such as CD30, CD40, IL-2R (CD25/CD122), IL-6R (CD126), IL-7R (CD127), TNF-R (CD120), TGF-β-R (CD105/endoglin), M-CSF-R (CD115), and SCF-R (CD117/c-kit receptor). All of these cytokines and cytokine receptors are implicated in the growth regulation of H-RS/ALCL cells, the histopathologic alterations in tissues, and the clinical manifestations in patients with Hodgkin's disease (HD) or ALCL. Many of these cytokines or cytokine receptors also play an important role in the pathogenesis of other types of lymphomas. In this review, we describe the cytokine or cytokine-receptor expression that is diacritic for H-RS/ALCL cells. The identification of such unique cytokine-cytokine receptor interactions is likely to explain the biologic property that distinguishes HD/ALCL from other types of lymphomas. These interactions include those of CD30L-CD30, CD40L-CD40, CD70-CD27, CD80/CD86-CD28, SCF-CD117, IL-9-IL9R, and IL-7-IL-7R. The H-RS/ALCL cells express IL-9 and two cytokine receptors, CD30 and CD117, which are observed infrequently in NHLs. Although IL-7 expression is not restricted to H-RS/ALCL cells, the expression of IL-7 in conjunction with IL-9 and/or CD117 may be regarded as unique for HD/ALCL because of an unusual combination and a synergistic activity among these cytokines. The expression of CD70 and CD80/CD86 (as cytokines) may exert a unique effect in HD because of intimate contact between H-RS cells and CD27/CD28-positive T cells. The expression of these costimulators (CD70 and CD80/CD86) and other adhesion/constimulator molecules such as CD54 and CD58, along with the secretion of soluble cytokines such as Il-1, IL-6, IL-7, or TNFs by H-RS/ALCL cells, could result in the profound T-cell proliferation often seen in lymph nodes involved by HD and some ALCL. On the other hand, the expression of CD30L and CD40L by surrounding T cells may affect the proliferation of H-RS/ALCL cells. The cytokine-cytokine receptor interaction between H-RS cells and T cells via direct cell-cell contact is bidirectional, a situation not commonly seen in NHLs.
ALPHA- AND BETA-D GALACTOSIDASE ACTIVITY OF RAT THYROID AND SPLEEN. A QUANTITATIVE STUDY.

SummaryRat thyroid gland and spleen contain levels of α and β-D galactosidases which show no significant sex-linked differences. We have no satisfactory explanation for the discrepancy in results from those of others, except that the parathyroid glands. very active for the two galactosidases, are closely related to the thyroid. It is suggested that careful dissection may be required to avoid inadvertent dilution or enrichment of enzyme source by adjacent anatomic structures. The quantitative data reported herein confirm previous histochemical observations of intense reactivity of rat thyroid gland for α- and β-D galactosidases. The differences in values obtained for spleen may reflect variations in numbers of heterophiles and mega-karyocytes which showed high α-D and β-D galactosidase activity by histochemical technics.
Germ line c-myc is not down-regulated by loss or exclusion of activating factors in myc-induced macrophage tumors.

Abstract As in tumors with c-myc chromosomal translocations, c-myc retrovirus-induced monocyte tumors constitutively express an activated form of c-myc (the proviral gene), whereas the normal endogenous c-myc genes are transcriptionally silent. Treatment of these retrovirus-induced tumor cells with a number of bioactive chemicals and growth factors that are known to induce c-myc expression in cells of the monocyte lineage failed to induce the endogenous c-myc gene. In contrast, the same treatments induced the c-fos gene in both tumors and a control macrophage line. To investigate c-myc suppression further, a normal copy of the human c-myc gene was introduced into tumor and control cell lines by using a retrovirus with self-inactivating long terminal repeats. This transduced normal gene was expressed at equivalent levels in all cells, regardless of the state of endogenous c-myc gene expression, and was strongly induced by agents that induce the normal gene in the control cells. These results indicate that the signal transduction pathways that normally activate the c-myc gene are functional in myc-induced tumor cells and suggest that endogenous c-myc is actively suppressed. An examination of the c-myc locus itself showed that the lack of transcriptional activity correlated with the absence of several prominent DNase I-hypersensitive sites in the 5'-flanking region of the gene but without loss of general DNase sensitivity. Furthermore, analysis of 22 methylation-sensitive restriction enzyme sites in the 5'-flanking region, first exon, and first intron indicated that the silent c-myc genes remained in the same unmethylated state as did actively expressed genes. Thus, c-myc suppression does not appear to result from the most frequently described mechanisms of gene inactivation.
Targeting the cAMP and Transforming Growth Factor-β Pathway Increases Proliferation to Promote Re-Epithelialization of Human Stem Cell-Derived Retinal Pigment Epithelium

Retinal pigment epithelium (RPE) cell integrity is critical to the maintenance of retinal function. Many retinopathies such as age-related macular degeneration (AMD) are caused by the degeneration or malfunction of the RPE cell layer. Replacement of diseased RPE with healthy, stem cell-derived RPE is a potential therapeutic strategy for treating AMD. Human embryonic stem cells (hESCs) differentiated into RPE progeny have the potential to provide an unlimited supply of cells for transplantation, but challenges around scalability and efficiency of the differentiation process still remain. Using hESC-derived RPE as a cellular model, we sought to understand mechanisms that could be modulated to increase RPE yield after differentiation. We show that RPE epithelialization is a density-dependent process, and cells seeded at low density fail to epithelialize. We demonstrate that activation of the cAMP pathway increases proliferation of dissociated RPE in culture, in part through inhibition of transforming growth factor-b (TGF-b) signaling. This results in enhanced uptake of epithelial identity, even in cultures seeded at low density. In line with these findings, targeted manipulation of the TGF-bpathway with small molecules produces an increase in efficiency of RPE re-epithelialization. Taken together, these data highlight mechanisms that promote epithelial fate acquisition in stem cellderived RPE. Modulation of these pathways has the potential to favorably impact scalability and clinical translation of hESC-derived RPE as a cell therapy.
Long-term regulation of Na(+)-H+ exchange in vascular smooth muscle cells: role of protein kinase C.

Regulation of intracellular pH (pHi) plays an important role in vascular smooth muscle cell (VSMC) contractile tone and growth. We have shown that pHi in proliferating VSMC is more alkaline (7.25) than in growth-arrested cells (7.10). To study the Na(+)-H+ exchanger in the growth-dependent regulation of VSMC pHi, ethylisopropylamiloride (EIPA)-sensitive Na+ influx was measured. Exposure of growth-arrested VSMC to 10% serum initially increased Na+ influx (145% of baseline at 30 min), which then decreased (52% of baseline at 24 h). Serum-induced alterations in the kinetic properties of the Na(+)-H+ exchanger were studied by analysis of its external Na+ binding site properties. Exposure of growth-arrested VSMC to 10% serum for 24 h increased the Km for external Na+ from 54 to 380 mM, with a change in the Vmax from 155 to 199 nmol Na+.mg protein-1.min-1. The change in Km was due to activation of protein kinase C (PKC). Phorbol 12,13-dibutyrate caused a 48% decrease in EIPA-sensitive influx, the inactive 4 alpha-phorbol 12,13-didecanoate had no effect, and the PKC inhibitor sphingosine reversed the effect. Therefore, the Na(+)-H+ exchanger in VSMC is regulated in a growth-dependent manner via PKC.
Identifying professional manpower for dietary departments.

For this manpower planning study, administrative abilities for nine types of dietetic positions in the hospital were identified. Hospital administrators provided information concerning chief dietitians, who, in turn, were surveyed concerning their staff positions. Three types of administrative ability—operational, personnel and managerial—were considered, each of which demands “human,” “conceptual,” and “technical” abilities in varying degree, depending on the level of responsibility.
The Mating System and Reproductive Life History of Female Timber Rattlesnakes in Northwestern Arkansas

Vertebrate mating strategies and life history patterns show great variation within and among species. Variation in reproductive tactics results from a combination of phylogenetic and environmental factors, and detailed natural and life history data among taxa are required to provide a comparative perspective or to infer evolutionary forces. Collection of such data in secretive species can often only be accomplished through long-term monitoring or the use of molecular tools. We used a combination of monitoring via radiotelemetry and microsatellite DNA markers to describe the reproductive ecology of a population of Timber Rattlesnakes, Crotalus horridus, in northwestern Arkansas. Female C. horridus in northwestern Arkansas were smaller at maturity and produce small litters compared to most estimates for other populations. Female snout–vent length and not the body condition of preparturient females was positively related to litter size and total litter mass. Both pregnant females and females found in associa...
Studies on orally available inhibitors of HIV protease: peptidyl aldehydes and trifluoromethyl ketones

Low-molecular-weight peptidyl aldehyde inhibitors of HIV protease that reach in vivo plasma concentrations after oral administration substantiailly in excess of the antiviral IC90 are described. We also report efforts to improve the potency and stability of these compounds that culminated in a series of peptidyl trifluoromethyl ketones with increased potency but decreased bioavailability.
Re-thinking America's Teacher Education Programs

ABSTRACTMore than ever before, our nation needs teachers who are not only motivated to teach but who are also properly educated, trained, and prepared for the many challenges that are facing our nation's K-12 public schools. The education departments and schools at our colleges and universities cannot continue to do business as usual—they need to adjust their teacher preparation programs to effectively support the changing times, and to provide our future teachers with a realistic and rigorous education. There is little or no disagreement among educators, social scientists, or anyone else for that matter, that great schools are the product of great teachers. It makes sense, therefore, to create a world-class teacher education and training program.
Good Morning, Midnight : Jean Rhys’s Melancholic Late Modernism

Jean Rhys’s fiction of the 1920s and 1930s offers an extended critical portrayal of down and out single women that circulate in a vicious market of spectacle, drink, fashion, and sex—only to lose. And Good Morning, Midnight (1939) serves as a particularly biting culmination of this ongoing engagement with the social limits of modernism’s culture of market fantasy. A novel that is alternately hilarious, surrealist, and just plain depressing, it satirizes the narcissistic promises of mass consumption discourses that had become thoroughly normalized by the late 1930s. Specifically, the novel shows how the consumer-focused economy operates around a form of cultural melancholia, where the continuous appeals to self-transformation both compensate for and recirculate the sense of accumulated loss that had become so central to the social structures of feeling by the late 1930s. In dramatizing this link between cultural melancholia and consumption, Rhys exposes a perverse internal limit to the ethos of self-fashioning. At the same time, the novel echoes “high” modernism’s transformative designs on market fantasy, suspending its hopes in a melancholic ambivalence tied to the repetition of fashion and consumption. This latter point, which I argue at the end of this chapter, makes Good Morning, Midnight a crucial, but neglected, text in recent discussions of late modernism.1
Rhonda’s Voice: And Gladly Would She Learn, and Gladly Teach

Looking back at my long career in education has been a daunting task. For each detail I incuded here several other stories emerged which made me laugh, become angry again, or sigh with regret. How we learn influences how we teach, and this story reveals that from my generational perspective. Teaching has been the heart of it all, and continual learning made it a challenging journey. Mentoring, being mentored, learning from others, and sharing that knowledge has given me joy, and I am grateful to mentors and students alike for the experiences.
Thoracic Paravertebral Nerve Blocks in Pediatric Patients: Safety and Clinical Experience

Thoracic paravertebral nerve blocks (PVNBs) provide excellent analgesia for many surgeries. The primary aim was to estimate the complication rate, and secondary aims were to provide information on the potential clinical application of PVNBs. Data on 2390 PVNBs were collected. A total of 625 catheters were performed on 468 patients, and 1765 single-injection PVNBs were performed on 403 patients. There was 1 case of local anesthetic systemic toxicity for a major complication rate of 1 per 2390 PVNBs. The minor complication rate was 13.2%. We demonstrate a low risk of complications in pediatric patients receiving PVNBs for various surgeries.
Income and child maltreatment in unmarried families: evidence from the earned income tax credit

This study estimates the associations of income with both (self-reported) child protective services involvement and parenting behaviors that proxy for child abuse and neglect risk among unmarried families. Our primary strategy follows the instrumental variables approach employed by Dahl and Lochner (2012), which leverages variation between states and over time in the generosity of the total state and federal earned income tax credit for which a family is eligible to identify exogenous variation in family income. As a robustness check, we also estimate standard OLS regressions (linear probability models), reduced form OLS regressions, and OLS regressions with the inclusion of a control function (each with and without family-specific fixed effects). Our micro-level data are drawn from the Fragile Families and Child Wellbeing Study, a longitudinal birth-cohort of relatively disadvantaged urban children who have been followed from birth to age nine. Results suggest that an exogenous increase in income is associated with reductions in behaviorally approximated child neglect and CPS involvement, particularly among low-income single-mother families.
Controls on Mountain Plant Diversity in Northern California: A 14,000-Year Overview

A network of eight Holocene paleoenvironmental records from lakes in the Klamath Mountains of Northern California provides insights on how diverse coniferous forests are maintained in the face of c...
Working with semiconductors

The semiconductor industry is one of the most dynamic business sectors to work in, having grown historically at a rate of some 18% per year. I joined the industry in 1984 after completing a PhD in solid-state physics and carrying out postdoctoral research at Stanford University. While I was at Stanford, I helped to develop surface analytical tools with scientists from NASA's Ames Research Center, who were keen to use them to develop new materials.
A topologically diverse family of fluoride channels

Dual-topology proteins are likely evolutionary antecedents to a common motif in membrane protein structures, the inverted repeat. A family of fluoride channels, the Flucs, which protect microorganisms, fungi, and plants against cytoplasmic fluoride accumulation, has representatives of all topologies along this evolutionary trajectory, including dual-topology homodimers, antiparallel heterodimers, and, in eukaryotes, fused two-domain proteins with an inverted repeat motif. Recent high-resolution crystal structures of dual-topology homodimers, coupled with extensive functional information about both the homodimers and two-domain Flucs, provide a case study of the co-evolution of fold and function.
Open Carpal Tunnel Release Outcomes: Performed Wide Awake versus with Sedation

Background Carpal tunnel release (CTR) is the most common surgery of the hand, and interest is growing in performing it under local anesthesia without tourniquet. To better understand differences, we hypothesized that patients undergoing CTR under wide-awake local anesthesia with no tourniquet (WALANT) versus sedation (monitored anesthesia care [MAC]) would not result in a difference in outcome. Methods Consecutive cases of electrodiagnostically confirmed open CTR across multiple surgeons at a single center were prospectively enrolled. Data included demographic data, visual analog scale, Levine-Katz carpal tunnel syndrome scale, QuickDASH questionnaire, customized Likert questionnaire, and complications. Results There were 81 patients enrolled in the WALANT group and 149 patients in the MAC group. There were no reoperations in either group or any epinephrine-related complications in the WALANT group. Disability and symptom scores did not differ significantly between WALANT and sedation groups at 2 weeks or 3 months. Average postoperative QuickDASH, Levine-Katz, and VAS pain scales were the same in both groups. Both groups of patients reported high levels of satisfaction at 91 versus 96% for the WALANT versus MAC groups, respectively ( p > 0.05). Patients in each group were likely to request similar anesthesia if they were to undergo surgery again. Conclusion Patients undergoing open CTR experienced similar levels of satisfaction and outcomes with either the WALANT or MAC techniques. There was no statistically significant difference between either group relative to the tested outcome measures. These data should facilitate surgeons and patients' choosing freely between WALANT and MAC techniques relative to complications and outcomes.
Inter dataset variability modeling for speaker recognition

We introduce a novel approach of addressing inter-dataset variability in the context of speaker recognition in a mismatched condition under the JHU-2013 domain adaptation challenge (DAC) framework. Previously, we took a subspace removal approach for inter-dataset variability compensation (IDVC) of within speaker variability. In this work we substitute subspace removal with incorporation of the variability into the Probabilistic Linear Discriminant Analysis (PLDA) model. We do that by introducing a novel optimality criterion which is minimizing the expected square error in estimation of the log-likelihood ratio of target trials when dataset-dependent PLDA models are replaced by a dataset independent PLDA model. The result we obtain is a correction term for the commonly estimated within speaker variability matrix. The correction term represents the normalized inter-dataset variability of the within speaker variability matrices. The proposed method outperforms the extended IDVC method on the DAC.
LARP1 functions as a molecular switch for mTORC1-mediated translation of an essential class of mRNAs

The RNA binding protein, LARP1, has been proposed to function downstream of mTORC1 to regulate the translation of 5’TOP mRNAs such as those encoding ribosome proteins (RP). However, the roles of LARP1 in the translation of 5’TOP mRNAs are controversial and its regulatory roles in mTORC1-mediated translation remain unclear. Here we show that LARP1 is a direct substrate of mTORC1 and Akt/S6K1. Deep sequencing of LARP1-bound mRNAs reveal that non-phosphorylated LARP1 interacts with both 5’ and 3’UTRs of RP mRNAs and inhibits their translation. Importantly, phosphorylation of LARP1 by mTORC1 and Akt/S6K1 dissociates it from 5’UTRs and relieves its inhibitory activity on RP mRNA translation. Concomitantly, phosphorylated LARP1 scaffolds mTORC1 on the 3’UTRs of translationally-competent RP mRNAs to facilitate mTORC1-dependent induction of translation initiation. Thus, in response to cellular mTOR activity, LARP1 serves as a phosphorylation-sensitive molecular switch for turning off or on RP mRNA translation and subsequent ribosome biogenesis. DOI: http://dx.doi.org/10.7554/eLife.25237.001
TRPV1-mediated Pharmacological Hypothermia Promotes Improved Functional Recovery Following Ischemic Stroke

Hypothermia shows promise for stroke neuroprotection, but current cooling strategies cause undesirable side effects that limit their clinical applications. Increasing efforts have focused on pharmacological hypothermia as a treatment option for stroke. Previously, we showed that activation of a thermoregulatory ion channel, transient receptor potential vanilloid 1 (TRPV1), by dihydrocapsaicin (DHC) produces reliable hypothermia. In this study, we investigate the effects of TRPV1-mediated hypothermia by DHC on long-term ischemic stroke injury and functional outcome. Hypothermia initiated at 3.5 hours after stroke significantly reduced primary cortical injury. Interestingly, hypothermia by DHC also significantly reduced secondary thalamic injury, as DHC-treated stroke mice exhibited 53% smaller thalamic lesion size. DHC-treated stroke mice further demonstrated decreased neuronal loss and astrogliosis in the thalamus and less thalamic fiber loss by diffusion tensor imaging (DTI). Importantly, a single 8 hour treatment of hypothermia by DHC after stroke provided long-term improvement in functional outcome, as DHC-treated mice exhibited improved behavioral recovery at one month post-stroke. These findings indicate that TRPV1-mediated hypothermia is effective in reducing both primary cortical injury and remote secondary thalamic injury, and a single treatment can produce persistent effects on functional recovery. These data highlight the therapeutic potential for TRPV1 agonism for stroke treatment.
Predictive analytics in reverse supply chain management commodity life expectancy for quality engineering

As the competitive market becomes more customized and the customer becomes more educated, companies are striving to sell quality products. Moreover, customer relationships are significantly influenced by after product-purchase service quality. Reverse Logistics is one such area, where there is ample room for improvisation. It deals with the process of product return from the customer to the manufacturer. The product maybe returned due to reasons like failure, product lifetime etc. It is different from traditional logistics where processes are carried out from manufacturer to final user stage only. It can be optimized and made predictive in nature to forecast the reverse flow of commodities. Conventionally, the commodities are sent back to the manufacturer upon encounter of failure. The products, under warranty period, are immediately replaced by the manufacturer. However, the quality of the service provided is deteriorating. With the advent of information age, it is possible to be prepared for tomorrow, today. By predicting the time of failure of a commodity, the manufacturer can retain service quality levels and help avoid customer churn. In Supply Chain Management(SCM), there is a plethora of data from different sources and in different formats. Big Data, Machine to Machine(M2M), IOT etc. provide a lot of scope into drawing clairvoyant insights. The aim of this paper is to discuss the methodology to forecast failure of a commodity. Such a model can not only help take prescriptive measures but also improve the service quality and protect a company's loyal customers. The paper also covers the process in all respects like the data extraction, management and cognitive approaches.
Coupled lateral-longitudinal vehicle dynamics and control design with three-dimensional state portraits

The dynamics of vehicles with pneumatic tyres are well-known to be non-holonomic, nonlinear, and subject to state bounds in order to remain on defined roadways. As such, it can be challenging to ap...
Tricyclic amine antidepressants suppress β‐lactam resistance in methicillin‐resistant Staphylococcus aureus (MRSA) by repressing mRNA levels of key resistance genes

Methicillin-resistant Staphylococcus aureus (MRSA) is the leading cause of recurrent infections in humans including endocarditis, pneumonia, and toxic shock syndrome. Novel therapeutics to treat MRSA and other resistant bacteria are urgently needed. Adjuvant therapy, which uses a non-toxic compound to repotentiate the toxic effects of an existing antibiotic, is an attractive response to the growing resistance crisis. Herein, we describe the evaluation of structurally related, FDA-approved tricyclic amine antidepressants that selectively repotentiate MRSA to β-lactam antibiotics. Our results identify important structural features of the tricyclic amine class for β-lactam adjuvant activity. Furthermore, we describe the mechanism of action for our lead compound, amoxapine, and illustrate that it represses the mRNA levels of key β-lactam resistance genes in response to β-lactam treatment. This work is novel in that it highlights an important class of small molecules with the ability to simultaneously inhibit production of both β-lactamase and penicillin binding protein 2a.
2-Transitive Designs

A great deal of work was done on 2-transitive groups during the last century and the beginning of this one. There has been a recent resurgence of interest in them for several reasons. First of all, many finite simple groups either have 2-transitive permutation representations or are closely related to groups that do. Also, recent work on finite simple groups has made the study of permutation groups more accessible. Finally, the close relationship between these groups and finite geometries has been recognized and has benefitted both group theory and geometry.
Diagnosis and Classification of the Schizophrenia Spectrum Disorders

The classification of schizophrenia related disorders have been evolving with advances in psychiatric research. In 1893 Emil Kraepelin distinguished dementia praecox from manic-depression, heralding the diagnosis of schizophrenia as a separate entity, but this distinction has since been challenged by data from genetic epidemiology. Over the past century, two major classification systems emerged: the American Psychiatric Association’s Diagnostic and Statistical Manual of Mental Disorders (DSM) and the World Health Organization’s International Statistical Classification of Diseases and Related Health Problems (ICD), of which new editions are expected to be soon published. The latter criteria are typically used in European countries, while the DSM criteria are used in the United States and the rest of the world, as well as prevailing in research studies. As with other psychiatric disorders, some have suggested that the diagnosis of psychotic disorders would be better addressed as individual dimensions of psychotic experiences (e.g. hallucinations and delusions) along which everyone varies, such that there is a spectrum or continuum rather than a cut-off between disorders and normality. Some disorders in the schizophrenia spectrum, such as schizoaffective disorder and schizotypal personality disorder have also been criticized for a relatively low interrater reliability, in part due to the difficulty of establishing fine grained timecourse information and to identifying subtle, sub-threshold psychotic type phenomena. This chapter discusses past and present diagnostic classifications of schizophrenia spectrum disorders, and research considerations for further improving our nosological system.
Knowledge-Based System Building Tools

An important landmark in the evolution of programming languages is the development of C++. C++ offers the advantages of object-oriented programming, while retaining the efficiency of C. However, C++ is a statically typed language and does not support the incremental addition of classes. Further, C++ does not come with a problem solving mechanism. COSMOS (C++ Object-oriented System Made fOr expert System development) was developed to address these deficiences. COSMOS is available gratis to universities and other non-profit research organizations.
Global Energy and Electricity Futures

It is impossible to look out into the next century without being struck by the looming presence of what we now call the “developing world.” It gives meaning to what Ben Wattenberg said, “that demographics is destiny.” Over the next half century, these nations will undertake an unprecedented, large-scale expansion in the use of commercial energy in their efforts to meet the basic needs of a rapidly growing population.
Precision gene editing technology and applications in nephrology.

The expanding field of precision gene editing is empowering researchers to directly modify DNA. Gene editing is made possible using synonymous technologies: a DNA-binding platform to molecularly locate user-selected genomic sequences and an associated biochemical activity that serves as a functional editor. The advent of accessible DNA-targeting molecular systems, such as zinc-finger nucleases, transcription activator-like effectors (TALEs) and CRISPR–Cas9 gene editing systems, has unlocked the ability to target nearly any DNA sequence with nucleotide-level precision. Progress has also been made in harnessing endogenous DNA repair machineries, such as non-homologous end joining, homology-directed repair and microhomology-mediated end joining, to functionally manipulate genetic sequences. As understanding of how DNA damage results in deletions, insertions and modifications increases, the genome becomes more predictably mutable. DNA-binding platforms such as TALEs and CRISPR can also be used to make locus-specific epigenetic changes and to transcriptionally enhance or suppress genes. Although many challenges remain, the application of precision gene editing technology in the field of nephrology has enabled the generation of new animal models of disease as well as advances in the development of novel therapeutic approaches such as gene therapy and xenotransplantation. The application of precision gene editing has great potential to accelerate basic research and advance clinical practice in nephrology. Here, the authors discuss this technology and the challenges and potential of genome editing in the kidney.
Expansion capacity of human muscle progenitor cells differs by age, sex, and metabolic fuel preference.

Activation of satellite cells and expansion of the muscle progenitor cell (MPC) population are essential to generate a sufficient number of cells to repair damaged skeletal muscle. Proliferating MP...
Thomas A. Swift's Electric Rifle Injuries to the Eye and Ocular Adnexa: The Management of Complex Trauma.

Purpose To report the ocular and adnexal injuries sustained by patients with Thomas A. Swift’s electric rifles (TASER; TASER International, Scottsdale, AZ), review the literature, and discuss the management of this complex trauma. Design Multicenter, retrospective case series and literature review. Participants Seventeen eyes of 16 patients (5 eyes of 5 patients treated at 3 institutions, and 12 eyes of 11 previously reported cases). Methods The clinical data of 17 eyes were pooled. Spearman’s correlation coefficient was used to assess the association between the extent of TASER injury and patient outcomes. Main Outcome Measures Extent of TASER injury (zone of injury, penetrating vs. perforating) and association with patient outcomes (visual acuity [VA] and retinal detachment [RD]). Results In our cohort, 4 patients were transported by law enforcement and 1 was transferred from a community hospital. Four patients were taken to the operating room for TASER removal and globe repair; 1 patient underwent removal in the emergency room. Of 17 pooled cases, 12 (71%) involved open-globe injury. Of these, there was a high rate of zone 3 injuries (100%; n = 12) and a high incidence of RD (73%; 8 of 11, eviscerated eye excluded). Among patients with closed-globe injury (n = 5), 1 patient demonstrated exudative RD and 1 patient demonstrated retinal dialysis with RD. Of 10 patients with RD, 1 (10%) achieved resolution with monitoring (exudative RD); 1 (10%) underwent cryopexy and pneumatic retinopexy; 3 (30%) underwent vitrectomy, and 5 (50%) with poor prognosis did not undergo vitreoretinal surgery. In the 3 patients who underwent vitrectomy, all 3 (100%) demonstrated redetachment resulting from proliferative vitreoretinopathy and required additional surgery. Visual acuity on presentation was significantly correlated with final VA (ρ = 0.783; P = 0.02). Men (94%) were more likely than women (6%) to sustain TASER trauma. Median age was 26 years. There was a 50% rate of loss to follow-up. Conclusions Thomas A. Swift’s electric rifle injuries to the eyes or ocular adnexa represent complex trauma. Zone 3 injuries are common. The visual prognosis is guarded, and eyes may require multiple surgeries to preserve vision. Patients are at high risk for loss to follow-up by way of incarceration.
Asymmetric spectral noise correlations in coherent Stokes and anti-Stokes Raman scatterings

As a diagonal projection of the traditional generalized two-dimensional correlation function, a one-dimensional second-order correlation function in the frequency domain is introduced. This function was applied in coherent Stokes and anti-Stokes Raman scattering (CSRS/CARS) processes. The experiment was performed by a high-average-power fiber amplified femtosecond laser system with a 1 MHz repetition rate. To measure spectral noise fluctuations, sets of 30 sample spectra of pyridine solution were recorded in the fast sequence mode. Experimental design combined with the use of appropriate notch filters allowed for simultaneous recording of the CARS/CSRS spectra. Asymmetry in the noise fluctuations between CARS and CSRS processes is revealed by both one- and two-dimensional (synchronous as well as asynchronous) noise correlation calculations, demonstrating a potential for a high-resolution spectroscopic tool.