cssi/SciSciGPT-SciSciNet huggingface dataset:
Small reservoir effects on headwater water quality in the rural-urban fringe, Georgia Piedmont, USA

Abstract Small reservoirs are prevalent landscape features that affect the physical, chemical, and biological characteristics of headwater streams. Tens of thousands of small reservoirs, often less than a hectare in size, were constructed over the past century within the United States. While remote-sensing and geographic-mapping technologies assist in identifying and quantifying these features, their localized influence on water quality is uncertain. We report a year-long physicochemical study of nine small reservoirs (0.15–2.17 ha) within the Oconee and Broad River Watersheds in the Georgia Piedmont. Study sites were selected along an urban-rural gradient with differing amounts of agricultural, forested, and developed land covers. Sites were sampled monthly for discharge and inflow/outflow water quality parameters (temperature, specific conductance, pH, dissolved oxygen, turbidity, alkalinity, total phosphorus, total nitrogen, nitrate, ammonium). While the proportion of developed land cover within watersheds had positive correlations with reservoir specific conductivity values, agricultural and forested land covers showed correlations (positive and negative, respectively) with reservoir alkalinity, total nitrogen, nitrate, and specific conductivity. The majority of outflow temperatures were warmer than inflows for all land uses throughout the year, especially in the summer. Outflows had lower nitrate concentrations, but higher ammonium. The type of outflow structure was also influential; top-release dams showed higher dissolved oxygen and pH than bottom-release dams. Water quality effects were still evident 250 m below the dam, albeit reduced.
Du Bois’ democratic defence of the value free ideal

Philosophers of science debate the proper role of non-epistemic value judgements in scientific reasoning. Many modern authors oppose the value free ideal, claiming that we should not even try to get scientists to eliminate all such non-epistemic value judgements from their reasoning. W. E. B. Du Bois, on the other hand, has a defence of the value free ideal in science that is rooted in a conception of the proper place of science in a democracy. In particular, Du Bois argues that the value free ideal must be upheld in order to, first, retain public trust in science and, second, ensure that those best placed to make use of scientifically acquired information are able to do so. This latter argument turns out to relate Du Bois’ position on the value free ideal in science to his defence of epistemic democracy. In this essay I elaborate, motivate, and relate to the modern debate, Du Bois’ under-appreciated defence of the value free ideal.
Record route IP traceback

The Internet introduces a variety of vulnerabilities that put the security and privacy of computer based systems under risk. One of the most perilous threats in the Internet is the Denial of Service (DoS) attack and its variants such as Distributed DoS (DDoS). In this work we propose a novel probabilistic packet marking scheme to infer forward paths from attacker sites to a victim site and enable the victim to delegate the defense to the upstream Internet Service Providers (ISPs). We exploit the record route feature of the IP protocol to implement our probabilistic packet marking scheme. Compared to the other techniques, our approach requires less many packets to construct the paths from attacker sites toward a victim site. Our results show that a victim site can construct the forward path from an attacker site after receiving 20.23 packets on the average under DoS attacks. Moreover, we construct the forward-paths graph from 5000 attacker sites toward the victim site by receiving 11.58 packets per attacker site, on the average.
A Safer Synthesis of 3,5-Bis(dinitromethyl)-1,2,4-triazole (BDT) and Its Mono and Di Salts: High-Performance Insensitive Energetic Materials

Design and synthesis of new insensitive high-performance energetic materials are significant because of the demands of both civilian and military applications. Now a straightforward route which does not necessitate the use of 1,1-diamino-2,2-dinitroethene (FOX-7) as a starting material has been developed to synthesize 3,5-bis(dinitromethyl)-1,2,4-triazole (BDT) and its mono and dianion salts. The X-ray structure of bis- triaminoguanidinium 3,5-bis(dinitromethyl)-1,2,4-triazolate (10) further confirms the structure of this dianion. The gem dinitro carbon results in higher packing coefficients and extensive hydrogen bonding interactions. The experimental densities range from 1.66 to 1.93 g cm−3, detonation velocities from 8347 to 9086 ms−1, and pressures from 27.3 to 38.7 GPa, respectively. Some of these values are superior to those of current benchmark explosives, such as 1,3,5-trinitroperhydro-1,3,5-triazine (RDX).
Off-policy reinforcement learning for distributed output synchronization of linear multi-agent systems

In this paper, off-policy reinforcement learning (RL) is used to find a model-free optimal solution to the H ∞ output synchronization of heterogeneous multi-agent discrete-time systems. First, the output synchronization problem is formulated as a set of local optimal tracking problems. It is shown that optimal local synchronization control protocols can be found by solving augmented game algebraic Riccati equations (GAREs). The solutions to the GAREs require the state of the leader for all agents and the knowledge of agent dynamics. To obviate this requirement, a distributed adaptive observer is designed to estimate the leader state for all agents without requiring complete knowledge of the leader dynamics. Moreover, off-policy RL algorithm is used to learn the solution to the GAREs using only measured data and without requiring the knowledge of the agent or the leader dynamics. In the proposed approach, in contrast to other model free approaches, the disturbance input does not need to be adjusted in a specific manner. A simulation example is given to show the effectiveness of the proposed method.
A Peculiar Cause of Anaphylaxis: No More steak?: The Journey to Discovery of a Newly Recognized Allergy to Galactose-alpha-1,3-galactose Found in Mammalian Meat

In recent years, a newly recognized allergic disease has been uncovered, and seemingly idiopathic causes of anaphylaxis now have an explanation. Individuals bitten by the lone star tick may develop IgE antibodies to the carbohydrate galactose-α-1,3-galactose (alpha-gal). Upon exposure of sensitized subjects to mammalian meat containing alpha-gal on glycoproteins or glycolipids, delayed anaphylaxis may ensue, often three to six hours after ingestion.1 Many of these individuals have negative allergy skin prick tests to meat, further obscuring the diagnosis. With the recent development of IgE alpha-gal tests, the clinical diagnosis can be confirmed in the laboratory.
Esophagus: Normal Anatomy, Function and Congenital Anomalies 7

The chapter will review the normal anatomy and function of the esophagus. The expected appearance of the esophagus on barium studies and computed tomography (CT) will be described. The technical details of performing these studies have been discussed elsewhere in this section. Congenital variants and anomalies affecting the esophagus are also included.
“No Matter How No Matter Where”: The Unlit in Samuel Beckett’s Not I and Stirrings Still

In the preface to Volume XIX of the Analecta Husserliana, Anna-Teresa Tymieniecka defines the purpose of our investigation of the Elements and clarifies the distinction to be made between the notion of the Elements that originated with the pre-Socratic philosophic tradition and that with which we are presently concerned: She defines the former as “the metaphysico-physicalistic principles of the composition of objective reality” and the latter as the “complexes of vital forces of Nature” operative within the human imagination.1 In her preface to the companion volume of the series (Volume XXIII), she alludes to our delving into the “locus where human genius reveals itself in the interplay of life-forces”2 and to our effort to open “a new access to the meaningfulness of the literary work by focusing upon its creation in this subliminal sphere in which the metamorphosis of the neutral order of Nature into life — into the felt resounding voice of human existence — takes place in the human creative act.”3
The DXA Report: What Every Referring Clinician Needs to Know

The report is the final sequence in the pathway of a patient’s bone density testing. After the technologist performs the test, the results are interpreted and a written report is generated by a clinician. The quality of the report can vary widely due to a lack of historical patient information and the fact that some “interpreters” simply pass on the data generated by the DXA computer and provide no clinical assessment or interpretation.
Oncology Patients Are High Cost Outliers in Total Joint Replacement Bundled Payment Systems.

Abstract Introduction In 2016, the Centers for Medicare and Medicaid Services began its first mandatory bundled payment program, the Comprehensive Care for Joint Replacement (CJR) model, which covers a 90-day episode of care. This study determined whether oncology patients enrolled in the CJR bundle incur higher hospital costs than patients with osteoarthritis (OA). Methods A retrospective review of all patients enrolled in the CJR bundled payments system from April 1, 2016 to June 31, 2018 at a single academic medical center. To determine whether tumor patients had higher total episode costs, this group was compared to patients diagnosed with osteoarthritis using a two-tailed t-test. To adjust for moderators of total hospital costs, we used generalized linear regression with a log-link, including multiple variables abstracted from chart review. Results 314 patients met inclusion criteria (12 primary or metastatic tumors, 302 OA). 58% of tumor patients were over the target price vs. 16% of OA patients. The mean tumor patient had $40,862 for total internal hospital costs compared to $16,356 in the OA group (p Conclusion Oncology patients enrolled in the CJR bundled payment model incur significantly higher costs and have higher cost variability than patients with osteoarthritis. We recommend that oncology patients be excluded from the CJR bundle.
Liveness in Interactive Systems.

Creating an artifact in front of public offers an opportunity to involve spectators in the creation process. For example, in a live music concert, audience members can clap, stomp and sing with the musicians to be part of the music piece. Live creation can facilitate collaboration with the spectators. The questions I set out to answer are what does it mean to have liveness in interactive systems to support large-scale hybrid events that involve audience participation. The notion of liveness is subtle in human-computer interaction. In this paper, I revisit the notion of liveness and provide definitions of both live and liveness from the perspective of designing interactive systems. In addition, I discuss why liveness matters in facilitating hybrid events and suggest future research works
Troglitazone and Prochloroperazine Repositioned As An Anti-Leukemia Stem Cell Drug Combination Using Chemical Genomics-Based Prediction

Abstract Abstract 1885 Current therapies used in the treatment of AML are highly toxic and have been shown to be ineffective at targeting AML stem cells (AML-SCs), which are chemoresistant and thus likely to provide a surviving reservoir of cells that drives AML relapse. The clinical relevance of AML-SCs in relapse is supported by studies indicating that higher AML-SC proportions at diagnosis and during minimal residual disease correlate with worse outcome. Previous studies have demonstrated that survival of AML-SCs is heavily dependent on both NFkappaB activation and redox homeostasis, which are simultaneously disrupted by the known anti-AML-SC compound, parthenolide (PTL). However, PTL represents a suboptimal drug based on its poor pharmacokinetics. Derivatives of PTL have been created and are currently in clinical trials. However, the process of taking pre-clinical findings to clinic is lengthy and success rates in this process are low. As therapies amenable to rapid clinical translation are urgently needed in AML, we sought to determine whether chemical genomics could be used to predict combinations of FDA-approved drugs that target AML-SCs. Previous studies have used chemical genomics to find PTL-like drugs by interrogating the Connectivity Map and Gene Expression Omnibus databases for drugs that perturb the cancer transcriptome so as to best mimic the transcriptional signature of PTL. However, no single agent found thus far is FDA approved. We hypothesized that we could extend the use this information to identify pairs of FDA approved drugs that together optimally mimic the anti-AML-SC transcriptional signature. To this end, we partitioned transcriptome changes caused by individual chemical perturbations of the Connectivity Map database into gene networks and sought to identify pairs of drugs that maximally perturbed the same networks as drugs targeting AML-SCs. This strategy revealed a combination consisting of the off-market anti-diabetes drug, troglitazone, and the anti-nausea drug, prochlorperazine. Individually, neither troglitazone nor prochlorperazine was able to target primary AML-SCs ex vivo, consistent with the inability of each drug to achieve a favorable PTL-like signature at transcriptomic level. Indeed, ex vivo exposure of primary AML-SCs to either troglitazone or prochloroperazine produced 99% and 87% mean viability, respectively, 24 hours post-treatment (N=3). In contrast, the combination of the two drugs reduced mean viability to 16% (p Disclosures: No relevant conflicts of interest to declare.
The role of PCDH19 in refractory status epilepticus.

Abstract PCDH19-Girls Clustering Epilepsy (GCE) is an epileptic syndrome with infantile onset, characterized by clustered and fever-induced seizures, often associated with intellectual disability (ID) and autistic features. Seizures clusters could progress into status epilepticus (SE) with different semiology, both convulsive and nonconvulsive SE (NCSE), and often refractory to conventional antiepileptic drugs. We reviewed literature on PCDH19-GCE, in order to define prevalence, semiology, treatments, and outcome of SE. We conducted a comprehensive review of the PCDH19-GCE literature on the public databases PubMed and EMBASE from January 2008 to July 2019. An overall number of 59 full-text articles were selected, retrieved, and assessed for eligibility. We collected 269 cases with PCDH19-GCE, in 85 of them, a history of SE was reported. Prevalence of SE in all selected series of PCDH19-GCE series is 31.5%. Data on SE were fully exhaustive in 21 cases. There was no gender difference in SE occurrence. Median age at first SE occurrence was 12 months (6 months–11 years). Semiology of SE was reported in 17 cases: it was convulsive in 15 and nonconvulsive in 2. Status epilepticus was refractory in 15 out of 21 cases (71.4%). Benzodiazepine was the most commonly used drug for SE. Alternative treatments with steroids and ketogenic diet were reported as well. We found a high prevalence of ID and autism (19 out of 21 patients, 90%). Despite the relatively high frequency of SE in those patients, there are few specific descriptions of the semiology, EEG pattern, and treatment approach. We strongly believe that a multicenter study looking specifically at SE characteristics might improve the knowledge and consequently the overall outcome. This article is part of the Special Issue “Proceedings of the 7th London-Innsbruck Colloquium on Status Epilepticus and Acute Seizures".
Optimization of Operational Decisions in Digital Advertising: A Literature Review

The digital advertising industry has witnessed an impressive explosion since its inception. With Internet advertising revenues already at over $200 billion, the projections are for continued growth. The format and technological underpinnings of digital advertising make it a fascinating subject of study for practitioners and academics alike, and distinguish it from traditional advertising in many ways. In contrast to traditional advertising, online advertising offers significantly more channels, a lower cost alternative, greater targeting and personalization capabilities, and dynamic pricing capabilities. While these digital technologies offer unprecedented opportunities to marketers to maximize the ROI on their marketing budgets, the data-rich environment also presents a unique set of managerial, operational, and intellectual challenges. In this chapter, we introduce the reader to some of these challenges. Our goal is to identify some of the salient operational challenges facing advertisers and publishers in this digital advertising environment, and summarize the state of the art of the published research that attempts to address these challenges. Our hope is that practitioners, academics, and graduate students will find this to be a valuable resource in their various endeavors.
Genetic Ablation of Hematopoietic Cell Kinase Accelerates Alzheimer’s Disease–Like Neuropathology in Tg2576 Mice

Microglial dysregulation, pertaining to impairment in phagocytosis, clearance and containment of amyloid-β (Aβ), and activation of neuroinflammation, has been posited to contribute to the pathogenesis of Alzheimer's disease (AD). Detailed cellular mechanisms that are disrupted during the disease course to display such impairment in microglia, however, remain largely undetermined. We hypothesize that loss of hematopoietic cell kinase (HCK), a phagocytosis-regulating member of the Src family tyrosine kinases that mediate signals from triggering receptor expressed on myeloid cells 2 and other immunoreceptors, impairs microglial homeostasis and Aβ clearance, leading to the accelerated buildup of Aβ pathology and cognitive decline during the early stage of neuropathological development. To elucidate the pivotal role of HCK in AD, we generated a constitutive knockout of HCK in the Tg2576 mouse model of AD. We found that HCK deficiency accelerated cognitive decline along with elevated Aβ level and plaque burden, attenuated microglial Aβ phagocytosis, induced iNOS expression in microglial clusters, and reduced pre-synaptic protein at the hippocampal regions. Our findings substantiate that HCK plays a prominent role in regulating microglial neuroprotective functions and attenuating early AD neuropathology.
15.1 A 5nm 135Mb SRAM in EUV and High-Mobility-Channel FinFET Technology with Metal Coupling and Charge-Sharing Write-Assist Circuitry Schemes for High-Density and Low-V MIN Applications

Despite recent advances, low-voltage operation remains one of the key approaches for power reduction. However, the continuous scaling of the SRAM bit cell, in advanced technologies, based on the transistor's minimum geometry is accompanied by increased random threshold voltage variations that limit the SRAM's minimum operating voltage (V MIN ). The introduction of FinFET transistors has provided better short channel effects and less random dopant fluctuation, compared to prior bulk CMOS technology. However, the quantization of transistor sizing continues to be a major challenge for high-density 6T SRAM design. Figure 15.1.1(a) shows the layout of a high-density 6T SRAM bit cell in a 5nm EUV and high-mobility channel FinFET technology. In order to achieve a compact bit-cell area, using FinFET technology, all transistors have to consist of a single fin. Figure 15.1.1(b) shows the SRAM bit-cell area scaling trend since 2011: area continues to scale, even as technology evolved into the sub-20nm era. This work reports a 0.021 µm2 high-density SRAM bit cell for a leading edge 5nm technology [1]. Figure 15.1.2(a) shows the SRAM voltage scaling trend: where the blue line indicates the V MIN of the SRAM bit cell without circuit assist and the red line indicates the V MIN with circuit assist. Write assist is the key enabler for lowering V DD operation in 5nm technology. Figure 15.1.2(b) shows a contention between pull-up (PU) and pass-gate (PG) transistors during a write operation. A stronger PU transistor yields higher read stability, but it degrades the write margin significantly and results in a contention write V MIN issue. In order to improve the write V MIN , the negative BL (NBL) and lower cell V DD (LCV) techniques have been proposed [2], [6]. However, the write-assist circuitry results in area overhead. In order to reduce the area of the assist circuitry, this work proposes NBL [7] and LCV with metal coupling/charge sharing capacitors to reduce the area overhead of the NBL-boosted and LCV charge-sharing capacitors. Furthermore, the flying BL (FBL) architecture [8] is also implemented to further reduce area.
Status and future directions of clinical trials in Alzheimer's disease

Amyloid-β (Aβ) senile plaques and neurofibrillary tangles of tau are generally recognized as the culprits of Alzheimer's disease (AD) and related dementia. About 25 years ago, the amyloid cascade hypotheses postulated a direct correlation of plaques with the development of AD, and it has been the dominant theory since then. In this period, more than 200 clinical trials focused mainly on targeting components of the Aβ cascade have dramatically failed, some of them in Phase III. With a greater than 99.6% failure rate at a cost of several billion from governments, industry, and private funders, therapeutic strategies targeting amyloid and tau are now under scrutiny. Therefore, it is time to reevaluate alternatives to targeting Aβ and tau as effective therapeutic strategies for AD. The diagnosis of AD is currently based on medical examination of symptoms including tests to assess memory impairment, attention, language, and other thinking skills. This is complemented with brain scans, such as computed tomography, magnetic resonance imaging, or positron emission tomography with the help of imaging probes targeting Aβ or tau deposits. This approach has contributed to the tunnel vision focus on Aβ and tau as the main culprits of AD. However, events upstream of these proteopathies (age-related impaired neuronal bioenergetics, lysosome function, neurotrophic signaling, and neuroinflammation, among others) are almost surely where the development of alternative therapeutic interventions should be targeted. Here, we present the current status of therapeutic candidates targeting diverse mechanisms and strategies including Aβ and tau, proteins involved in Aβ production and trafficking (ApoE, α/β/γ-secretases), neuroinflammation, neurotransmitters, neuroprotective agents antimicrobials, and gene and stem cell therapy. There are currently around 33 compounds in Phase III, 78 in Phase II, and 32 more in Phase I trials. With the current world health crisis of increased dementia in a rapidly aging population, effective AD therapies are desperately needed.
Lytic Cell Death Mechanisms in Human Respiratory Syncytial Virus-Infected Macrophages: Roles of Pyroptosis and Necroptosis

Human respiratory syncytial virus (RSV) is the most common cause of viral bronchiolitis and pneumonia in infants and children worldwide. Inflammation induced by RSV infection is responsible for its hallmark manifestation of bronchiolitis and pneumonia. The cellular debris created through lytic cell death of infected cells is a potent initiator of this inflammation. Macrophages are known to play a pivotal role in the early innate immune and inflammatory response to viral pathogens. However, the lytic cell death mechanisms associated with RSV infection in macrophages remains unknown. Two distinct mechanisms involved in lytic cell death are pyroptosis and necroptosis. Our studies revealed that RSV induces lytic cell death in macrophages via both of these mechanisms, specifically through the ASC (Apoptosis-associated speck like protein containing a caspase recruitment domain)-NLRP3 (nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3) inflammasome activation of both caspase-1 dependent pyroptosis and receptor-interacting serine/threonine-protein kinase 3 (RIPK3), as well as a mixed lineage kinase domain like pseudokinase (MLKL)-dependent necroptosis. In addition, we demonstrated an important role of reactive oxygen species (ROS) during lytic cell death of RSV-infected macrophages.
Cognitive behavioral social rhythm group therapy versus present centered group therapy for veterans with posttraumatic stress disorder and major depressive disorder: A randomized controlled pilot trial.

Abstract Background Cognitive Behavioral Social Rhythm Group Therapy (CBSRT) is a chronobiologically-informed group therapy designed to stabilize social rhythms in veterans with comorbid combat-related PTSD and major depressive disorder (MDD). This randomized controlled pilot trial is the first to examine feasibility and preliminary efficacy of group CBSRT as compared to group Present Centered Therapy (PCT), a well-characterized active attention, psychotherapy condition. Methods A total of 43 male veterans with combat-related PTSD, MDD, and disruptions in sleep or daily routine were randomly assigned to CBSRT or PCT. Therapy was provided weekly in a group modality for 12 weeks. Follow-up feasibility and gold-standard PTSD, MDD, and subjective/objective sleep assessments were conducted at post-treatment, 3 months, and 6 months post-treatment. Results Feasibility results demonstrated that veterans assigned to CBSRT had higher rates of attendance than veterans assigned to PCT. Both CBSRT and PCT were associated with improvements in PTSD and MDD symptoms, sleep efficiency, and number of awakenings; there were no differences between group therapies on these indices. Veterans in the CBSRT group had a greater reduction in the number of nightmares than veterans in the PCT group. Limitations Preliminary results must be qualified by the small sample size. Conclusions Group CBSRT may be more feasible for veterans than PCT. Both CBSRT and PCT were associated with improvements in psychiatric symptoms with few differences between conditions. CBSRT is a promising new group therapy that may help address the high-rate of PTSD therapy attrition in combat veterans. Clinical trial registration NCT00984698.
Comparison of dalbavancin to standard-of-care for outpatient treatment of invasive Gram-positive infections

Abstract Objective: To assess the efficacy and safety of dalbavancin compared to standard-of-care (SOC) or vancomycin and daptomycin in invasive infections due to suspected or confirmed Gram-positive organisms. Methods: Retrospective cohort of adults who received dalbavancin or SOC on discharge or as an outpatient from 12/2016 to 11/2019. Indications were osteoarticular infection (OAI), infective endocarditis (IE), or other bloodstream infection (BSI). Primary endpoint was 90-day infection-related readmission (IRR); secondary endpoints included time-to-IRR, frequency of adverse drug events (ADEs), and all-cause readmission and mortality. Results: 215 patients were included: 70 (33%) receiving dalbavancin, and 145 (67%) receiving SOC. Indications were OAI (47%), IE (27%), and other BSI (26%). OAI was more common in patients on dalbavancin compared with those receiving SOC (70% vs. 37%, P [7] , [8] , [9] , [10] , [11] , [12] , [13] , [14] , [15] , [16] , [17] vs. 13 [9] , [10] , [11] , [12] , [13] , [14] , [15] , [16] , [17] , [18] , [19] , P=0.021). IRR incidence was 17% for dalbavancin patients and 28% for SOC patients. Dalbavancin use was independently associated with lower IRR (adjusted odds ratio [adjOR], 0.10; 95% confidence interval [CI], 0.04-0.31). There was longer median (IQR) time-to-IRR in the dalbavancin group (43 [30-87] vs. 23 [11 -63] days, P=0.039), but no differences in all-cause readmission or mortality. Treatment-related ADE incidence was 3% and 14% for the dalbavancin and SOC groups, respectively (P=0.013). Infusion reactions (1/2) and catheter-related complications (1/2) were the most common dalbavancin ADEs; catheter-related complications (14/21), nephrotoxicity (3/21), rhabdomyolysis (2/21), and rash (2/21) were the most common SOC ADEs. Conclusions: Dalbavancin use was associated with lower 90-day IRR, a shorter hospital LOS prior to therapy, and longer time-to-IRR compared with SOC.
Verrucous Carcinoma Arising Secondary to Diabetic Foot Lesions: A Systematic Review of the Literature

Verrucous carcinoma is classically considered a variant of squamous cell carcinoma, most commonly occurring in the oral cavity in association with snuff and chewed tobacco. However, the association between verrucous carcinoma of the foot and diabetes is less well known. This study presents a systematic review of all articles containing the search term “verrucous carcinoma” and “diabetic foot ulcer” in the abstract or title that have been published in PubMed before September 2020. The requirement for inclusion in our report were that the patient data had been documented in a case‐related manner and the patient diagnosed with verrucous carcinoma secondary to diabetic foot lesion. Seven descriptions of verrucous carcinoma presenting in patients with diabetic foot ulcers were presented across six case reports, and clinical case descriptions are collected here along with treatment outcomes, where available, and discussion of common mimics of verrucous carcinoma of the foot. Due to treatability and potential for extensive invasion of local structures requiring resection with wide margins, verrucous carcinoma should be carefully considered in the differential diagnosis of a warty foot lesion in the setting of the diabetic foot.
Multiple mechanisms impact fluconazole resistance of mutant Erg11 proteins in Candida glabrata

Abstract Azoles remain the most common used antifungal drugs for invasive candidiasis worldwide. They specifically inhibit the fungal lanosterol α-14 demethylase enzyme, which is commonly referred to as Erg11 in fungi. Inhibition of Erg11 ultimately leads to a reduction in ergosterol production, an essential fungal membrane sterol. Many Candida species, such as Candida albicans, develop mutations in this enzyme which reduces the azole binding affinity and results in increased azole resistance. Candida glabrata is also a pathogenic yeast that has a low intrinsic susceptibility to azole drugs and easily develops elevated resistance. These azole resistant mutations are almost exclusively found to cause hyperactivity of the Pdr1 transcription factor and rarely lie within the ERG11 gene. Here, we generated C. glabrata ERG11 mutations that were analogous to azole resistance associated mutations in C. albicans ERG11. Three different Erg11 forms (Y141H, S410F, and the corresponding double mutant (DM)) conferred azole resistance in C. glabrata with the DM Erg11 form causing the strongest phenotype. The DM Erg11 also induced cross-resistance to amphotericin B and caspofungin. The azole resistance caused by the DM allele of ERG11 imposed a fitness cost that was not observed with hyperactive PDR1 alleles. These data support the view that C. glabrata does not typically acquire ERG11 mutations owing to growth defects associated with these lesions while hyperactive PDR1 alleles have no obvious growth issues. Understanding the physiology linking ergosterol biosynthesis with Pdr1-mediated regulation of azole resistance is crucial for ensuring the continued efficacy of azole drugs against C. glabrata. Importance Azole drugs target the Erg11 enzyme and lead to a reduction in fungal ergosterol, a vital sterol in yeast. Mutations in Erg11 are common among azole resistant Candida albicans clinical isolates, but not in C. glabrata, a major human pathogen. In this study, we showed that ERG11 mutations were tolerated in C. glabrata, and these mutations could confer azole resistance. We also showed that ERG11 mutations were less efficient in inducing azole resistance in comparison to PDR1 gain-of-function mutations, the most common mutation found among C. glabrata azole resistant clinical isolates. Our data suggest that growth issues associated with azole resistant alleles of ERG11 in C. glabrata may limit the appearance of this class of resistant strains. Furthermore, these data illustrate the deep connections between ergosterol biosynthesis and regulation of membrane transporter proteins via Pdr1 and the ergosterol-responsive transcription factor Upc2A.
Differences in information accessed in a pharmacologic knowledge base using a conversational agent vs traditional search methods.

INTRODUCTION Clinicians rely on pharmacologic knowledge bases to answer medication questions and avoid potential adverse drug events. In late 2018, an artificial intelligence-based conversational agent, Watson Assistant (WA), was made available to online subscribers to the pharmacologic knowledge base, Micromedex®. WA allows users to ask medication-related questions in natural language. This study evaluated search method-dependent differences in the frequency of information accessed by traditional methods (keyword search and heading navigation) vs conversational agent search. MATERIALS AND METHODS We compared the proportion of information types accessed through the conversational agent to the proportion of analogous information types accessed by traditional methods during the first 6 months of 2020. RESULTS Addition of the conversational agent allowed early adopters to access 22 different information types contained in the 'quick answers' portion of the knowledge base. These information types were accessed 117,550 times with WA during the study period, compared to 33,649,651 times using traditional search methods. The distribution across information types differed by method employed (c2 test, P < .0001). Single drug/dosing, FDA/non-FDA uses, adverse effects, and drug administration emerged as 4 of the top 5 information types accessed by either method. Intravenous compatibility was accessed more frequently using the conversational agent (7.7% vs. 0.6% for traditional methods), whereas dose adjustments were accessed more frequently via traditional methods (4.8% vs. 1.4% for WA). CONCLUSION In a widely used pharmacologic knowledge base, information accessed through conversational agents versus traditional methods differed. User-centered studies are needed to understand these differences.
Solid rocket motor internal ballistics using an enhanced surface-vorticity panel technique

This work explores the use of surface-mesh flow solvers to model solid rocket internal ballistics with arbitrary grain geometry. Specifically, a surface-vorticity approach, originally intended for external flow applications, is adapted for internal flow analysis using boundary conditions that are suitable for solid rocket motors. In this study, an enhanced panel code is shown to be capable of resolving internal rocket flowfields with a striking level of fidelity and with such a degree of computational efficiency to make it valuable in the conceptual and preliminary design of rocket motors. In this process, the vortex paneling approach embodied within FlightStream® is refined using boundary conditions appropriate for solid rocket rotational flows. The simulation results are then compared to existing analytical solutions for cylindrical and planar chamber configurations exhibiting small taper angles and uniform headwall injection. For a more realistic validation case, the space shuttle's reusable solid rocket motor (RSRM) is examined. Guided by the analytical models, simple rotational and compressibility corrections are incorporated into the solver, and the results are subsequently compared to two other computational models and experimental measurements gathered from qualification motors. For the basic configurations, our results are shown to agree well with theoretical predictions. For the RSRM case, the corrected solution agrees well with the validation data in the first half of the motor; however, it becomes less robust in the aft region unless a recirculation zone boundary patch is applied; the latter approximates the added vorticity introduced by intersegmental gaps and the submerged nozzle effects.
Determining the Sequence of Ball-Point Pen Writings—A New Method?

Examiners of questioned documents are frequently faced with the problem of determining the sequence of crossed lines. The answer to the question of line sequence can be of immense importance. To determine which of two intersecting pen strokes was made first may ultimately decide the outcome of a contested court case, or even negate the necessity of a trial. The disclosure of a cleverly perpetrated fraud or the sustaining of a genuine writing in controversy may result from such a determination.
Cholera toxin: genetic analysis, regulation, and role in pathogenesis.

One of the most well studied and earliest recognized mechanisms of bacterial pathogenesis is the production of potent exotoxins. Protein toxins are clearly involved in the pathogenesis of a wide variety of bacterial diseases affecting mankind. These include cholera, diphtheria, pertussis, anthrax, dysentery, tetanus, gas gangrene, and opportunistic infections caused by Pseudomonas aeruginosa, Staphylococcus aureus, Streptococcus pyogenes, and Clostridium difficile. Even Escherichia coli does on occasion possess the necessary genetic information for the production of several protein toxins which can enhance its pathogenicity. Yet, as of the date of this review, a detailed understanding of the molecular events involved in the genetic regulation of any one of these bacterial toxins has not been achieved. Moreover, the specific advantage or benefit imparted to the microbe by the production of these often lethal proteins has never been clearly elucidated.
'Assessing' Discrimination: The Influence of Race in Residential Property Tax Assessments

In this Article, I document evidence that residential property in majority-minority neighborhoods is assessed at higher effective rates than like property in majority-white neighborhoods. I examine data on sales price and assessed value for more than fourteen hundred homes sales in New Haven, Connecticut from 2000-2001. My chief finding is that residents of minority neighborhoods - namely, African American and Latino - face assessments that are significantly higher than the market value of their residences, while residents of majority white neighborhoods are assessed at significantly less than market value. As a solution to assessment discrimination, I propose that assessments be meted out not on the purported market value of the underlying residence as is the case currently in most jurisdictions, but based on the actual cash costs of making home purchases.
Minimax and Triality Theory in Nonsmooth Variational Problems

Dual extremum principles and minimax theory are investigated for nonsmooth variational problems. The critical points of the Lagrangian L(u, p*) for fully nonlinear (both geometrically and physically nonlinear) systems are clarified. We proved that the critical point of L(u, p*) is a saddle point if and only if the Gao-Strang’s gap function is positive. In this case, the system has only one dual problem. However if this gap function is negative, the critical point of the Lagrangian is a so-called super-critical point which is equivalent to the Auchmuty’s anomalous critical point in geometrically linear systems. We discover that in this case, the system may have more than one set of primal-dual problems. The critical point of the Lagrangian either minimizes or maximizes both primal and dual problems. Application in nonconvex finite deformation theory is illustrated and a pure complementary energy is proposed. It is shown that the dual Euler-Lagrange equation of nonlinear variational boundary value problem is an algebraic equation. An analytic solution is obtained for a non-convex, unilateral variational problem.
On the privacy of web search based on query obfuscation: a case study of TrackMeNot

Web Search is one of the most rapidly growing applications on the internet today. However, the current practice followed by most search engines - of logging and analyzing users' queries - raises serious privacy concerns. One viable solution to search privacy is query obfuscation, whereby a client-side software attempts to mask real user queries via injection of certain noisy queries. In contrast to other privacy-preserving search mechanisms, query obfuscation does not require server-side modifications or a third party infrastructure, thus allowing for ready deployment at the discretion of privacy-conscious users. In this paper, our higher level goal is to analyze whether query obfuscation can preserve users' privacy in practice against an adversarial search engine. We focus on TrackMeNot (TMN) [10,20], a popular search privacy tool based on the principle of query obfuscation. We demonstrate that a search engine, equipped with only a short-term history of a user's search queries, can break the privacy guarantees of TMN by only utilizing off-the-shelf machine learning classifiers.
Temporal interactions in the cat visual system. III. Pharmacological studies of cortical suppression suggest a presynaptic mechanism.

When tested with pairs of brief visual stimuli, neurons of the primary visual cortex of the cat show a long-lasting, orientation-selective suppression, termed “paired-pulse suppression.” The hypothesis that this suppression is due to GABAA-mediated inhibition was tested by performing temporal interaction tests before, during, and after iontophoretic application of the selective antagonist bicuculline methiodide (BMI). In keeping with previous reports, BMI elevated the spontaneous and evoked firing rates of cortical neurons, and altered basic receptive field properties. Under the influence of BMI, most neurons showed a reduced or abolished selectivity for stimulus orientation and direction of movement. The effects on orientation selectivity required higher ejection currents than did the effects on directional selectivity. At high ejection currents, most cells did lose selectivity for the orientation of a moving stimulus, but retained some selectivity for the orientation of a stationary stimulus. BMI, even at very high ejection currents, did not abolish paired-pulse suppression. In some cells, BMI enhanced or prolonged paired-pulse suppression. In further experiments, temporal interaction tests were performed in which one or the other of the component stimuli was replaced with a pharmacological stimulus (a pulse of glutamate or potassium). A pharmacological stimulus did not produce suppression of the response to a subsequent visual stimulus, nor did a visual stimulus suppress the response to a subsequent pharmacological stimulus. Paired-pulse suppression occurred only when both stimuli were visual. Taken together with previous results, the present data indicate that paired-pulse suppression is most likely due to a presynaptic mechanism.
Preliminary Design of a 100 W 1.8 K to 4.7 K Regenerative Magnetic Refrigerator

An Active Magnetic Regenerator (AMR.) is designed to operate in the 1.8 K to 4.7 K range using a particle bed of gadolinium gallium garnet (GGG) as the magnetic material and liquid helium as the heat transfer fluid. A detailed mode] of the design is described in which all relevant physical and material properties are included. Using conservative operating parameters, a 100 W device is possible with COP efficiency relative to Carnot in the 40 to 50% range and a bed volume of less than 5 liters. In addition to its compact nature and high efficiency, the design offers the advantages of having only two moving parts operating at low speed, and operating pressure greater than one atmosphere.
Common Comorbidities among Multiple Sclerosis Patients in the United States: An Analysis of In-patient Hospitalizations (P5.154)

OBJECTIVE: To identify the common primary admitting diagnoses among hospitalized MS patients in the United States (US). BACKGROUND: The burden of hospitalizations in the US is unknown. DESIGN/METHODS: Using the Nationwide Inpatient Sample for 2001-2010, all patients with primary or secondary diagnosis of MS were identified. The primary admitting diagnoses for all MS patients were identified and compared with that of non-MS patients. Trends in hospitalizations were studied in specific age groups (1-9yrs, 10-19yrs, 20-29yrs, 30-39yrs, 40-49yrs, 50-59yrs, 60-69yrs,70-79yrs, 80-84yrs and 蠅85yrs), and population level rates were obtained and compared with non-MS patients to obtain rate ratios (RR). RESULTS: A total of 1,240,410 MS patients were identified representing 4 out of every 1000 US hospital admissions, with an estimated female/male ratio of 2.72/1. The median age for MS hospitalizations was 53 years (Interquartile-range=18). The majority of all MS hospitalizations occurred in the 30-69 year age bracket (82.17%). The average length of in-patient hospital stay for MS patients compared to the non-MS population was 5.8 vs. 4.5 days (p<0.001), and more MS patients had Medicare insurance (50.36% vs. 42.24%, p<0.001). Overall, conditions such as urinary tract infections (UTI) - (RR11.43, p<0.001), septicemia (RR8.53, p<0.001), pneumonia (RR2.84, p<0.001), chronic skin ulcers (RR20.64, p<0.001), and lower limb and femoral neck fractures (RR2.86, p<0.001) were higher among MS patients. Notably, 4% of young MS patients (1-19 years of age) were admitted for epilepsy (4%). Among MS patients 蠅65 years of age,the most common primary non-MS admitting diagnoses included UTI (11%), septicemia (10%) and pneumonia (9%). CONCLUSIONS: Our results show that MS brings patients into hospital at a younger age, keeps patients longer in the hospital and uses more Medicare resources than the general population. The highest burden is among older individuals, for whom the most common non-MS admitting conditions include UTIs, septicemia, and pneumonia. These findings are particularly significant in light of accumulating data that systemic infection and inflammation can drive MS relapses. Disclosure: Dr. Asemota has nothing to disclose. Dr. Wang has nothing to disclose. Dr. Selvarajah has nothing to disclose. Dr. Hui has nothing to disclose. Dr. Schneider has nothing to disclose. Dr. Venkatesan has nothing to disclose.
Facile nanoparticle dispersion detection in energetic composites by rare earth doped in metal oxide nanostructures

The segregation and agglomeration of nanoparticles dispersed in polymer matrices play important roles in nanocomposite performance. A method of rapid and simultaneous visualization of macroscopic and submicron particle dispersion properties is presented, based on nanoparticle luminescence induced by europium doping. The luminescence intensity of polymer composites containing Eu-doped TiO2 nanoparticle catalysts varied with the nanoparticle agglomerate size between 90 nm and 10 μm, and with concentration variations from segregation. These variations were detected by photoluminescence spectroscopy and visible-light photography, making this a facile characterization method for bulk composites without affecting the nanoparticle performance.
Location of Ti Catalyst in the Reversible AlH3 Adduct of Triethylenediamine

AlH3, a metastable binary hydride with a hydrogen content of 10.1 wt % hydrogen and a density of 1.48 g/mL, is a potential lightweight hydrogen storage system for transportation applications. A key component to understanding the discharge and uptake of hydrogen is the role of the Ti dopant in these processes. Here, the morphological and compositional changes caused by the synthesis and dehydriding of the AlH3 adduct of triethylenediamine was determined by using a combination of scanning electron and scanning transmission electron microscopy as well as X-ray energy dispersive spectroscopy. It is shown that there is significant loss of the added Ti at each step in the synthesis; the Ti agglomerates in the Al particles, causing enrichment, and the amount of Ti needed to catalyze the activity is on the order of 0.4 at.%, which amounts to approximately a 90% reduction from the amount added.