cssi/SciSciGPT-SciSciNet huggingface dataset:
Moving forward to address key unanswered questions on targeting PD-1/PD-L1 in cancer: limitations in preclinical models and the need to incorporate human modifying factors

The tremendous clinical success of immune checkpoint inhibition (ICI), particularly targeting the programmed cell death protein 1 (PD-1)/programmed death-ligand 1/2 (PD-L1/2) pathway, has resulted in application to multiple cancers, as a monotherapy and as a companion to both conventional and novel agents. Despite this, the precise mechanisms underlying the anti-tumor effects of PD-1/PD-L1 blockade remain unclear. Emphasis has centered on its reversal of tumor-specific CD8+ T-cell exhaustion, although many cell types and processes are likely impacted. Due to the complex and pervasive roles of PD-1/PD-L1 on T-cell biology, including on initial T-cell priming, PD-1 blockade likely affects all aspects of T- cell responses, and these other effects may be even more critical for durable anti-tumor responses. Delineating these complex interactions necessitates in vivo modeling. By far, the healthy, young and inbred laboratory mouse, transplanted with an extensively cultured tumor cell line, has been the predominant preclinical model used to assess potential therapeutic efficacies. However, these mouse models often do not adequately reflect the tumor progression and cellular and genetic heterogeneity found within human cancers. Furthermore, laboratory mice also present with a vastly restricted immune profile compared to humans. This commentary discusses some of the critical questions that need to be addressed to optimize the use of ICI as well as caveats and limitations for consideration when extrapolating preclinical mouse data to the human cancer scenario.
Treatment of Secondary Chorea: A Review of the Current Literature

Background: Chorea consists of involuntary movements affecting the limbs, trunk, neck or face, that can move from one body part to another. Chorea is conceptualized as being “primary” when it is attributed to Huntington’s disease (HD) or other genetic etiologies, or “secondary” when it is related to infectious, pharmacologic, metabolic, autoimmune disorders, or paraneoplastic syndromes. The mainstay of the secondary chorea management is treating the underlying causative disorder; here we review the literature regarding secondary chorea. We also discuss the management of several non-HD genetic diseases in which chorea can be a feature, where metabolic targets may be amenable to intervention and chorea reduction. Methods: A PubMed literature search was performed for articles relating to chorea and its medical and surgical management. We reviewed the articles and cross-references of pertinent articles to assess the current clinical practice, expert opinion, and evidence-based medicine to synthesize recommendations for the management of secondary chorea. Results: There are very few double-blind randomized controlled trials assessing chorea treatments regardless of etiology. Most recommendations are based on small open-label studies, case reports, and expert opinion. Discussion: Treatment of secondary chorea is currently based on expert opinion, clinical experience, and small case studies, with limited evidence-based medical data. When chorea is secondary to an underlying infection, medication, metabolic abnormality, autoimmune process, or paraneoplastic illness, the movements typically resolve following treatment of the underlying disease. Tardive dyskinesia is most rigorously studied secondary chorea with the best evidence-based medicine treatment guidelines recommending the use of pre-synaptic dopamine-depleting agents. Even though there is an insufficient pool of EBM, small clinical trials, case reports, and expert opinion are valuable for guiding treatment and improving the quality of life for patients with chorea. Highlights: There is a dearth of well-controlled studies regarding the treatment of chorea. Expert opinion and clinical experiences are fundamental in guiding chorea management and determining successful treatment. In general, secondary chorea improves with treating the underlying medical abnormality; treatments include antibiotics, antivirals, immunosuppression, dopamine depleting agents, chelation, and supportive care.
Rupture-dependent breakdown energy in fault models with thermo-hydro-mechanical processes

Abstract. Substantial insight into earthquake source processes has resulted from considering frictional ruptures analogous to cohesive-zone shear cracks from fracture mechanics. This analogy holds for slip-weakening representations of fault friction that encapsulate the resistance to rupture propagation in the form of breakdown energy, analogous to fracture energy, prescribed in advance as if it were a material property of the fault interface. Here, we use numerical models of earthquake sequences with enhanced weakening due to thermal pressurization of pore fluids to show how accounting for thermo-hydro-mechanical processes during dynamic shear ruptures makes breakdown energy rupture-dependent. We find that local breakdown energy is neither a constant material property nor uniquely defined by the amount of slip attained during rupture, but depends on how that slip is achieved through the history of slip rate and dynamic stress changes during the rupture process. As a consequence, the frictional breakdown energy of the same location along the fault can vary significantly in different earthquake ruptures that pass through. These results suggest the need to reexamine the assumption of predetermined frictional breakdown energy common in dynamic rupture modeling and to better understand the factors that control rupture dynamics in the presence of thermo-hydro-mechanical processes.
A Cautionary Tale of an Emergency Cerebrovascular Procedure in the COVID-19 Era.

Abstract The coronavirus disease 2019 pandemic has had an impact on system processes, with airway management being significantly affected. A 37-year-old woman diagnosed with stroke was found to have a filling defect at the origin of the right internal carotid artery. She was taken to the operating room urgently for carotid endarterectomy. The procedure was uneventful; however, anaphylaxis developed on extubation, subsequently attributed to sugammadex. Institutional policies and limited resources resulted in delayed reintubation. Fortunately, she did not have lasting deficits, but this highlights the potential of current policies to lead to complications and the need to improve policies to minimize harm.
Engineered influenza virions reveal the contributions of non-hemagglutinin structural proteins to vaccine mediated protection

The development of improved and universal anti-influenza vaccines would represent a major advance in the protection of human health. In order to facilitate the development of such vaccines, understanding how viral proteins can contribute to protection from disease is critical. Much of the previous work to address these questions relied on reductionist systems (i.e. vaccinating with individual proteins or VLPs that contain only a few viral proteins); thus we have an incomplete understanding of how immunity to different subsets of viral proteins contribute to protection. Here, we report the development of a platform in which a single viral protein can be deleted from an authentic viral particle that retains the remaining full complement of structural proteins and viral RNA. As a first study with this system, we chose to delete the major IAV antigen, the hemagglutinin protein, to evaluate how the other components of the viral particle contribute en masse to protection from influenza disease. Our results show that while anti-HA immunity plays a major role in protection from challenge with a vaccine-matched strain, the contributions from other structural proteins were the major drivers of protection against highly antigenically drifted, homosubtypic strains. This work highlights the importance of evaluating the inclusion of non-HA viral proteins in the development of broadly efficacious and long-lasting influenza vaccines.ImportanceInfluenza virus vaccines currently afford short-term protection from viruses that are closely related to the vaccine strains. There is currently much effort to develop improved, next-generation influenza vaccines that elicit broader and longer-lasting protection. While the hemagglutinin protein is the major viral antigen, in this work, we developed an approach with which to evaluate the contributions of the non-hemagglutinin proteins to vaccine mediated protection. Our results indicate that other structural proteins together may help to mediate broad antiviral protection and should be considered in the development of more universal influenza vaccines.
Decreased Alcohol Consumption in an Implementation Study of Computerized Brief Intervention among HIV Patients in Clinical Care.

This prospective, nonrandomized implementation study evaluated a computerized brief intervention (CBI) for persons with HIV (PWH) and heavy/hazardous alcohol use. CBI was integrated into two HIV primary care clinics. Eligible patients were engaged in care, ≥ 18 years old, English speaking, endorsed heavy/hazardous alcohol use on the Alcohol Use Disorders Identification Test-C (AUDIT-C). Two 20-min computerized sessions using cognitive behavioral techniques were delivered by a 3-D avatar on touch screen tablets. Of 816 eligible AUDIT-C scores, 537 (66%) resulted in CBI invitation, 226 (42%) of invited patients enrolled, and 176 (78%) of enrolled patients watched at least one session. CBI enrollment was associated with a significant average reduction of 9.1 drinks/week (95% CI − 14.5, − 3.6) 4–12 months post-enrollment. Among those who participated in one or both sessions, average reduction in drinks/week was 11.7 drinks/week (95% CI − 18.8, − 4.6). There was corresponding improvement in AUDIT-C scores. Overall patients reported high levels of intervention satisfaction, particularly among older and Black patients. These promising results point to a practical intervention for alcohol reduction in this vulnerable patient population with elevated rates of heavy/hazardous drinking. Future research should examine strategies to increase initial engagement, strengthen intervention effects to increase the number of patients who achieve non-hazardous drinking, and examine the duration of therapeutic effects.
Endoscopic revision of gastrojejunal anastomosis for the treatment of dumping syndrome in patients with Roux-en-Y gastric bypass: a systematic review and meta-analysis

Dumping syndrome is a known complication of Roux-en-Y gastric bypass (RYGB). Recently, endoscopic gastrojejunal anastomosis (GJA) revision has been employed as a treatment option. The primary aim of this study was to perform a systematic review and meta-analysis for the role of endoscopic GJA revision in patients with RYGB for the treatment of dumping syndrome. Search strategies were developed for PubMed, EMBASE, Web of Science, and Cochrane Library databases from inception through December 2020 in accordance with PRISMA and MOOSE guidelines. Pooled proportions with rates estimated using random effects models were used. Outcomes included pooled technical success, clinical success, adverse events, and rate of reintervention. Heterogeneity was assessed with I2 statistics and publication bias by funnel plot using Egger and Begg tests. Six studies (n = 263 patients; 60.25% female) were included (1 prospective and 5 retrospective). Mean age was 46.27 ± 2.54 years. Average patient weight was 95.59 ± 4.78 kg, BMI of 41.43 ± 3.07 kg/m2, and pre-procedure GJA size of 32.23 ± 8.68 mm. Pooled technical and clinical success was 98.15% and 89.5%. Among studies reporting Sigstad scores, endoscopic GJA revision resulted in a significant improvement [mean Sigstad score difference of − 9.96 (95% CI, − 19.951 to − 0.975); P < 0.03]. Mean procedure time was 37.12 ± 10.40 min with an intra-procedural adverse event rate of 2.42%. Over a mean follow-up of 8.03 ± 6.87 months, post-procedure adverse events occurred in 2.96% of patients with a reintervention rate of 11.54%. This systematic review and meta-analysis suggests that endoscopic GJA revision appears an effective and safe treatment for dumping syndrome.
Understanding Sibling Relationships: A Hermeneutic Approach

This chapter summarizes an exploratory study of relationships between adult siblings in one large family. The study used a hermeneutic approach (Glaser, 1978; Glaser & Strauss, 1967; Strauss, 1987) in an attempt to determine how adult siblings perceived and interpreted their relationships within a family context. This exploratory approach allows insights, hypotheses, and tentative conclusions about family functioning to emerge; they can be tested more rigorously in further studies employing larger samples of smaller families more typical of present and future generations.
Atmospheric Methane: An Introduction

Methane is a greenhouse gas thought to be second only to CO2 as an agent of future global warming. The increasing trend is the single most important reason for the current interest in methane It is the foundation for much of the research on methane during the past decade, particularly on the global budget, which is tied directly to explaining why it is increasing. Figure 1 (a-f) shows the concentration and trends of methane over the recent decades and back to a thousand years. I want to describe briefly the progress towards the understanding of global budgets and trends, and to provide a guide to the book.
Addiction treatment provider attitudes on staff capacity and evidence-based clinical training: results from a national study.

This national study of addiction-treatment organizations’ implementation of evidence-based practices examines: (1) organizational/leadership factors associated with director (n = 212) attitudes regarding staff resistance to organizational change, and (2) organizational/staff factors associated with staff (n = 312) attitudes regarding evidence-based clinical training. Linear regression analyses, controlling for type of treatment unit, leadership/staff characteristics and organizational readiness to change, identified that directors who perceived their organization needed more guidance and had less staff cohesion and autonomy rated staff resistance to organizational change significantly higher. Staff with higher levels of education and greater agreement that their organization supported change had greater preference for evidence-based trainings. Federal addiction treatment policy should both promote education and training of treatment staff and organizational development of treatment CBOs. (Am J Addict 2011;00:1–14)
The Quotation Behavior of ECNs and Nasdaq Market Makers

We examine the impact of three Nasdaq rule changes on some aspects of market quality. In particular we investigate the quotation behavior of market makers following the reduction in tick size from eighths to sixteenths on June 2, 1997; the direct impact of including electronic communication network (ECN) quotes in the calculation of inside Nasdaq quotes; and the efficacy of the Actual Size Rule (ASR) during a time of market stress. We find that following the tick size reduction Nasdaq market makers again appear to be avoiding odd ticks (now odd sixteenths), but traders entering orders on ECNs appear to be more likely to use all ticks. We also find that ECNs establish the "inside market" and hence reduce trading costs for the public about 19% of the time. Finally, our findings suggest that the ASR led to a significant reduction in bid liquidity during the sharp market downturn of October 27-28, 1997. From a regulatory perspective, the results of our study suggest that while some of the market reforms have improved market quality, there are still major impediments to quote price competition and certain changes may have reduced liquidity. The nature of the data used in this study allows us to test three competing hypotheses for odd tick avoidance: natural "clustering" behavior; preferencing of order flow; and "tacit conspiracy" among oligopolistic market makers. We find no support for the natural clustering hypothesis and some inconsistencies with the preferencing hypothesis. Our findings are generally consistent with the tacit collusion hypothesis.
The low salt syndrome. An extreme example in heart failure.

Abstract Hyponatremia in congestive heart disease is discussed and the case of a patient with severe heart failure showing a serum sodium of 89 mEq. per L. is reported. This value returned to near normal levels with fluid restriction and diuresis. This case re-emphasizes that the “low salt syndrome” or hyponatremia of hemodilution is part of the clinical picture of congestive heart failure. Salt replacement is contraindicated. The serum sodium level returns to normal when vigorous treatment is directed to the heart failure and the mobilization of edema fluid. Administration of sodium chloride to correct the chemical “abnormality” may cause deterioration of the patient's condition.
Emerging roles for protein histidine phosphorylation in cellular signal transduction: lessons from the islet β-cell

Protein phosphorylation represents one of the key regulatory events in physiological insulin secretion from the islet β-cell. In this context, several classes of protein kinases (e.g. calcium-, cyclic nucleotide- and phospholipid-dependent protein kinases and tyrosine kinases) have been characterized in the β-cell. The majority of phosphorylated amino acids identified include phosphoserine, phosphothreonine and phosphotyrosine. Protein histidine phosphorylation has been implicated in the prokaryotic and eukaryotic cellular signal transduction. Most notably, phoshohistidine accounts for 6% of total protein phosphorylation in eukaryotes, which makes it nearly 100-fold more abundant than phosphotyrosine, but less abundant than phosphoserine and phosphothreonine. However, very little is known about the number of proteins with phosphohistidines, since they are highly labile and are rapidly lost during phosphoamino acid identification under standard experimental conditions. The overall objectives of this review are to: (i) summarize the existing evidence indicating the subcellular distribution and characterization of various histidine kinases in the islet β-cell, (ii) describe evidence for functional regulation of these kinases by agonists of insulin secretion, (iii) present a working model to implicate novel regulatory roles for histidine kinases in the receptor-independent activation, by glucose, of G-proteins endogenous to the β-cell, (iv) summarize evidence supporting the localization of protein histidine phosphatases in the islet β-cell and (v) highlight experimental evidence suggesting potential defects in the histidine kinase signalling cascade in islets derived from the Goto-Kakizaki (GK) rat, a model for type 2 diabetes. Potential avenues for future research to further decipher regulatory roles for protein histidine phosphorylation in physiological insulin secretion are also discussed.
In vitro activity of dimethylarsinic acid against human leukemia and multiple myeloma cell lines

Purpose Arsenic trioxide (As2O3), an inorganic arsenic compound, has recently been approved for the treatment of relapsed or refractory acute promyelocytic leukemia. However, systemic toxicity associated with As2O3 treatment remains a problem. Inorganic arsenic is detoxified in vivo by methylation reactions into organic arsenic compounds that are less toxic.
Extensive Exserohilum infection in a burn patient

Dematiaceous fungi are an uncommon cause of skin infections and rarely cause widespread cutaneous infections except in immunosuppressed patients.1, 2 We report a case caused by Exserohilum rostratum in a patient with extensive burns and no exposure to compounded corticosteroids.
Gender differences in life expectancy with and without disability among older adults in Ecuador

Abstract Background Knowledge on disability's impact among older women and men in Ecuador is limited. This paper provides gender-specific estimates of disability prevalence, life expectancy with and without disability, and the factors associated with gender differences in disability at older age in Ecuador (2009–2010). Methods Data from the Health, Well-Being, and Aging Survey (SABE) Ecuador 2009 was used. Participants were 4480 men and women aged 60 and over. Life expectancy with and without disability was calculated using the Sullivan method. Logistic regression analyses were used to explore gender differences in disability prevalence. Two disability measures, indicating limitations in activities of daily living (ADL) and instrumental activities of daily living (IADL), were used. Results 60-year-old women in Ecuador can expect to live 16.3 years without ADL limitations compared to 16.9 years for men. Life expectancy without IADL limitations was 12.5 years for women and 15.5 years for men. At age 60, women's length of life with ADL and IADL disability was higher (7.9 years for women vs. 4.9 years for men with ADL, and 11.7 years for women vs. 6.3 years for men with IADL). After controlling for socioeconomic characteristics, chronic conditions and lifestyle factors, gender differences in ADL disability were not statistically significant. However, older women were 58% more likely (OR = 1.58, 95% CI 1.27, 1.95) to report having IADL limitations than men, even after including control variables. Conclusion Interventions should tackle chronic disease, physical inactivity, and socioeconomic differences to reduce women's vulnerability to disability in older age.
For which graphs does every edge belong to exactly two chordless cycles

A graph is 2-cycled if each edge is contained in exactly two of its chordless cycles. The 2-cycled graphs arise in connection with the study of balanced signing of graphs and matrices. The concept of balance of a $\{0,+1,-1\}$-matrix or a signed bipartite graph has been studied by Truemper and by Conforti et al. The concept of $\alpha$-balance is a generalization introduced by Truemper. Truemper exhibits a family ${\cal F}$ of planar graphs such that a graph $G$ can be signed to be $\alpha$-balanced if and only if each induced subgraph of $G$ in ${\cal F}$ can. We show here that the graphs in ${\cal F}$ are exactly the 2-connected 2-cycled graphs.
A comparison of selected morphological and chemical methods for measuring neuron activity in the supraoptic nucleus of dehydrated rats.

A comparison of results of measuring supraoptic neuron activity was made in normal and in dehydrated rats by the following methods; (1) Measuring the nucleolar diameter of the neurons with a filar micrometer, with an image splitting eyepiece and, with the latter instrument, using the “comparative technique”—all three methods yielded statistically significant differences. (2) Measuring the concentration of cresyl violet in the nucleoli with a microspectrophotometer—a statistically significant difference was found. Also included for comparison were the results of a previous experiment in which the ribonucleic acid and succinic dehydrogenase content of the supraoptic nucleus was measured with a spectrophotometer following chemical extraction. The RNA was found to increase significantly but not the succinic dehydrogenase. Of the methods used for measuring nucleolar diameters the “comparative technique” appeared to be the most rapid from the practical viewpoint.
Photoacoustic tomography: fundamentals, advances and prospects

Optical microscopy has been contributing to the development of life science for more than three centuries. However, due to strong optical scattering in tissue, its in vivo imaging ability has been restricted to studies at superficial depths. Advances in photoacoustic tomography (PAT) now allow multiscale imaging at depths from sub-millimeter to several centimeters, with spatial resolutions from sub-micrometer to sub-millimeter. Because of this high scalability and its unique optical absorption contrast, PAT is capable of performing anatomical, functional, molecular and fluid-dynamic imaging at various system levels, and is playing an increasingly important role in fundamental biological research and clinical practice. This review discusses recent technical progress in PAT and presents corresponding applications. It ends with a discussion of several prospects and their technical challenges.
Effects of a Living Nonfreeze-Dried Lactobacillus acidophilus Culture on Performance, Egg Quality, and Gut Microflora in Commercial Layers,

Abstract A living Lactobacillus acidophilus culture was incorporated into the diets of two commercial strains of laying hens at three geographical locations to study its effect on performance, egg quality, egg weight, and alterations in gut microflora. The Lactobacillus culture was added at the rate of .0125, .0375, or .0625% of the diet. Feeding the Lactobacillus resulted in significantly increased egg production at one location (Arizona), a numerical improvement at the second (Florida), and no difference at die third location (South Dakota). An across-trial analysis of all egg production data provided a statistical advantage to adding Lactobacillus to diets of commercial layers. One location (Arizona) reported a significant response in feed efficiency (kg/doz eggs) at lower Lactobacillus levels. The other locations were unable to statistically demonstrate a similar response. The addition of Lactobacillus did not alter egg quality or egg weights. At two locations, Lactobacillus treated hens consumed more feed than nontreated hens during warmer months. An early increase in Lactobacillus acidophilus organisms accompanied by a drastic reduction in coliforms in selected gastrointestinal sections was measured in one study (Florida). A later measurement of the microflora did not substantiate this observation.
A Comparison of Survival Among Dialytic Therapies of Choice: In-Center Hemodialysis Versus Continuous Ambulatory Peritoneal Dialysis at Home

Analyses were performed on a series of 2,754 dialysis patients between the ages of 20 and 60 years whose endstage renal disease (ESRD) therapy started in Michigan from 1980 through 1987 with the selection of either center hemodialysis (CH) or continuous ambulatory peritoneal dialysis (CAPD). The dialytic treatment at 6 months after first ESRD therapy was selected as the dialytic "treatment of choice" for each patient. Analyses of subsequent survival showed lower death rates for black patients than for white patients with hypertension (P
Comments on CFD code performance on scalable architectures

We comment on the current performance of computational fluid dynamics codes on a variety of scalable computer architectures. The performance figures are derived from both the finite-volume and finite-element methodologies, and encompass shared, virtual shared, and distributed memory architectures, as exemplified by the SGI Origin series, CM5, and the CRAY T3D/E family, respectively.
The adenine pocket of a single catalytic site is derivatized when the bovine heart mitochondrial F1-ATPase is photoinactivated with 4-amino-1-octylquinaldinium

The bovine heart mitochondrial F1-ATPase (MF1) is reversibly inhibited in the dark by 4-amino-1-octylquinaldinium (AOQ) with an I0.5 value of 48 microM. When irradiated in the presence of AOQ, MF1 is photoinactivated with an apparent Kd of 12 microM. About 1.1 mol of [3H]AOQ were incorporated per mol of MF1 on complete photoinactivation. Fractionation of a cyanogen bromide digest of MF1 photolabeled with [3H]AOQ followed by fractionation of peptic digests of partially purified cyanogen bromide fragments led to isolation of two CNBr/peptic fragments labeled with 3H. Sequence analysis of the labeled peptides revealed that one contained residues 423-441 of the beta subunit. A gap in position 2 of the sequence indicates that beta Phe424 is derivatized. The phenyl side-chain of this residue is part of a pocket that binds the adenine moiety of ATP or ADP at catalytic sites. The other peptide, which was labeled to a greater extent, contained residues 342-358 of the beta subunit, but in this case, no gap was found in the sequence indicating that the derivatized amino-acid side-chain might not have survived the conditions of automatic Edman degradation. This peptide contains beta Tyr345, the side-chain of which is also a component of the pocket that binds the adenine moiety of ATP or ADP to catalytic sites. However, for the reason stated, there is no direct evidence that beta Tyr345 is labeled in this peptide.
Simulation tool for assessing the release and environmental distribution of nanomaterials.

An integrated simulation tool was developed for assessing the potential release and environmental distribution of nanomaterials (RedNano) based on a life cycle assessment approach and multimedia compartmental modeling coupled with mechanistic intermedia transport processes. The RedNano simulation tool and its web-based software implementation enables rapid “what-if?” scenario analysis, in order to assess the response of an environmental system to various release scenarios of engineered nanomaterials (ENMs). It also allows for the investigation of the impact of geographical and meteorological parameters on ENM distribution in the environment, comparison of the impact of ENM production and potential releases on different regions, and estimation of source release rates based on monitored ENM concentrations. Moreover, the RedNano simulation tool is suitable for research, academic, and regulatory purposes. Specifically, it has been used in environmental multimedia impact assessment courses at both the undergraduate and graduate levels. The RedNano simulation tool can also serve as a decision support tool to rapidly and critically assess the potential environmental implications of ENMs and thus ensure that nanotechnology is developed in a productive and environmentally responsible manner.
Heritability of Mastitis Score in Pacific Northwest Dairy Herds

Abstract Dairy Herd Improvement Association records of Holsteins in the Pacific Northwest were used to estimate heritabilities and correlations between milk yield, fat yield, fat percentage, and mastitis score. Effects of sire and lactation number were important for all traits except lactation number for fat percentage. Average mastitis score as well as frequency of elevated tests increased with parity. Paternal half-sister analysis showed that heritabilities of milk yield, fat yield, and fat percentage decreased with age averaging .33, .28, and .47 for first records and .29, .20, and .3 3 for last records. Heritability of mastitis score increased slightly with age averaging .10 for first records and .11 for last records. Milk yield and fat yield showed small genetic correlations of .05 and .07 with mastitis score. Pearson and Spearman correlation coefficients were computed between regressed least square estimates for sires derived for six independent sets of daughters. Pearson correlations between mastitis scores of first and last lactations were .19 and .34, whereas corresponding average Spearman correlations were .11 and .29. These low correlations between sire rankings in different data sets correspond closely with the low heritabilities for mastitis score.
Local Control and Survival in Early Stage Breast Cancer

: The two dominant views of the 20th century as to how and when breast cancer spreads are usually designated as the “Halstedian” and “Fisherian” theories. They entail different therapeutic strategies as well. While the Halstedian theory is generally agreed to be incorrect, neither is the Fisherian view adequate either. In particular, the latter theory does not explain why postmastectomy radiotherapy for nodepositive patients, postoperative radiotherapy for patients treated with breast-conserving surgery, and effective axillary treatment improve diseasefree and overall survival rates to a degree comparable to those absolute improvements achieved with the use of systemic therapy in node-negative patients. These results seem more compatible with what has become known as the “spectrum” theory. Most patients will desire the small increases in freedom from distant failure and overall survival resulting from techniques that improve local-regional control, provided the risk of morbidity is kept low. Nonetheless, the magnitude of the benefits of improved local-regional control has not been fully established in many situations. At some point these benefits may be so small that a significant proportion of patients will not find the potential morbidity of treatment justifiable. Hence it is reasonable to conduct further studies examining this question, although in practice this may be difficult to do.
The lesbian and gay liberation movement in the Presbyterian Church (U.S.A.), 1974-1996.

Abstract Since its founding in 1974, Presbyterians for Lesbian & Gay Concerns (PLGC) has led the movement toward full participation and membership for lesbian and gay people in the Presbyterian Church (U.S.A.). This is a story of that movement, told by a participant. It traces the development of current antigay policies in the church in 1976-78 in response to the first openly gay candidate for the ministry, PLGC's efforts to overturn these policies at annual General Assemblies, the growth of the pro-gay More Light Churches movement among Presbyterian congregations, the increasing number of antigay ecclesiastical court cases, study and dialogue on lesbian and gay issues across the denomination, and controversies over same-gender marriage, all culminating in the 1996 General Assembly, which endorsed civil rights for lesbian and gay couples, but also voted to send the controversial issue of lesbian and gay ordination to the 171 regional presbyteries of the church for an up or down vote. The battle for lesbia...
Virtual 3D bone fracture reconstruction via inter-fragmentary surface alignment

This paper presents a system for virtual reconstruction of comminuted bone fractures. The system takes as input a collection of bone fragment models represented as surface meshes, typically segmented from CT data. Users interact with fragment models in a virtual environment to reconstruct the fracture. In contrast to other approaches that are either completely automatic or completely interactive, the system attempts to strike a balance between interaction and automation. There are two key fracture reconstruction interactions: (1) specifying matching surface regions between fragment pairs and (2) initiating pairwise and global fragment alignment optimizations. Each match includes two fragment surface patches hypothesized to correspond in the reconstruction. Each alignment optimization initialized by the user triggers a 3D surface registration which takes as input: (1) the specified matches and (2) the current position of the fragments. The proposed system leverages domain knowledge via user interaction, and incorporates recent advancements in surface registration, to generate fragment reconstructions that are more accurate than manual methods and more reliable than completely automatic methods.
Bottom boundary layer spectral dissipation estimates in the presence of wave motions

Abstract Turbulence measurements are an essential element of the Sediment TRansport Events on Shelves and Slopes experiment (STRESS). Sediment transport under waves is initiated within the wave boundary layer at the seabed, at most a few tens of centimeters deep. The suspended load is carried by turbulent diffusion above the wave boundary layer. Quantification of the turbulent diffusion active above the wave boundary layer requires estimates of shear stress or energy dissipation in the presence of oscillating flows. Measurements by Benthic Acoustic Stress Sensors of velocity fluctuations were used to derive the dissipation rate from the energy level of the spectral inertial range (the -5/3 spectrum). When the wave orbital velocity is of similar magnitude to the mean flow, kinematic effects on the estimation techniques of stress and dissipation must be included. Throughout the STRESS experiment there was always significant wave energy affecting the turbulent bottom boundary layer. Lumley and Terray [(1983) Journal of Physical Oceanography, 13, 2000–2007] presented a theory describing the effect of orbital motions on kinetic energy spectra. Their model is used here with observations of spectra taken within a turbulent boundary layer which is affected by wave motion. While their method was an explicit solution for circular wave orbits aligned with mean current we extrapolated it to the case of near bed horizontal motions, not aligned with the current. The necessity of accounting for wave orbital motion is demonstrated, but variability within the field setting limited our certainty of the improvement in accuracy the corrections afforded.
Delivery of gastroschisis patients before 37 weeks of gestation is associated with increased morbidities

Abstract Background Despite advances in the care of neonates with gastroschisis, patients present with significant morbidities. Preterm delivery of neonates with gastroschisis is often advocated to avoid the intestinal damage that may be sustained with prolonged exposure to amniotic fluid. However, preterm delivery may impose additional morbidities to this disease process. Methods We conducted a retrospective review of patients with gastroschisis born from 1989 to 2007. Demographic and clinical data were collected. Preterm healthy neonates, with gestational age from 26 to 36 weeks, were used as controls. Results Preterm infants with gastroschisis had a 14 times higher risk for any of the recorded morbidities. As compared to term neonates with gastroschisis, preterm neonates with gastroschisis had a higher rate of sepsis, longer duration to reach full enteral feedings, and longer length of stay. Although the preterm infants with gastroschisis were less likely to be small for gestational age at birth, they were as likely as the term infants with gastroschisis to have failure to thrive at discharge and had a greater drop in weight percentile during hospitalization. Conclusions Preterm delivery should be avoided because there is no clear benefit to the gut in avoiding derivative injuries. Meticulous attention should be given to the nutritional needs of patients with gastroschisis.
PD09-08: Combined Inhibition of mTORC1 with Temsirolimus and HER2 with Neratinib: A Phase I/II Study in Patients with Metastatic HER2−Amplified or Triple-Negative Breast Cancer.

Background: Hyperactivation of the PI3K-AKT-mTOR pathway is a postulated mechanism of resistance to anti-HER2 therapies and has also been described in triple-negative breast tumors. In HER2−amplified (HER2+) laboratory models, inhibition of this pathway induces activation of upstream receptor tyrosine kinases such as HER3. In triple-negative breast cancer (TN), HER1 overexpression has been identified and models show sensitivity to combined HER1 and mTOR inhibition. We hypothesize that dual inhibition of the PI3K pathway, HER1/2, and induced HER3 may be highly effective in patients with HER2+ or TN breast cancer (BC). This phase I/II trial is designed to determine the tolerability and possible efficacy of the mTOR inhibitor temsirolimus (T) plus the HER1/2 inhibitor neratinib (N) in patients with trastuzumab-refractory, HER2+ or TN BC. We will also explore mutational activation of the PI3K pathway in trastuzumab-refractory tumors as it relates to response to the T-N combination. Methods: The phase I dose-escalation study evaluated T (flat dose IV weekly) plus N (240 mg oral daily) in patients with metastatic HER2+ or TN BC. Cycle length was 4 weeks. Phase I end points included definition of maximum tolerated dose (MTD) and response rate (RR) per RECIST. The phase II study has a Simon two-stage design and evaluates the HER2+ and TN patients separately. Phase II endpoints include progression free survival and duration of response. Response was evaluated radiographically every 8 weeks, toxicity assessed every 2 weeks. All patients underwent biopsy of metastatic disease for biomarker assessment. Activating mutations in PIK3CA were assayed using the Sequenom MassARRAY system. Expression of PTEN was assessed by immunohistochemistry utilizing a published scoring system. Results: The phase I study enrolled 8 HER2+ patients who received a median of 5 (1-13) cycles of therapy. All patients had received trastuzumab and a median of 5.5 (2-12) prior lines of therapy. Frequent treatment-related grade 2 events were: hyperglycemia (4/8), elevated CPK (3/8), diarrhea (2/8), and rash (2/8). Grade 3 diarrhea was the dose-limiting toxicity. Other grade 3 toxicity was hyperglycemia (1/8); hematologic toxicities were not observed. The MTD of temsirolimus with neratinib is 8 mg IV weekly. Six patients treated at MTD were evaluable for response; 4 patients had PR, 1 had SD for a RR of 67%. PI3K pathway activation, through PIK3CA mutational activation or PTEN loss, was identified in 4/6 tumors analyzed and did not preclude response to temsirolimus and neratinib. Updated results reflecting the phase II patients will be reported. Conclusions: Temsirolimus plus neratinib is active in trastuzumab-refractory HER2+ patients. The phase II study is ongoing and additional efficacy and safety data in both HER2−amplified and triple-negative breast cancer patients will be presented. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr PD09-08.
Virginia's Approach to Evaluation of Concrete Resistant to Alkali-Silica Reactions

Beginning in the late 1980s, the Virginia Department of Transportation (VDOT) observed that concrete made with aggregate containing micro-crystalline, strained, or highly fractured quartz was failing earlier than expected due to alkali-silica reactions (ASR). These reactive constituents are widespread in the aggregate resources available for use in Virginia. Difficulties have been encountered in accurately classifying aggregates with regard to their potential reactivity. Consequently, VDOT instead is attempting to identify and use cementitious materials that prevent or hinder ASR. These materials, pozzolans and slag, have been shown to reduce both ASR and permeability, resulting in a more durable concrete. Two newly developed tests were used to evaluate the effects of cementitious materials (ASTM C1260 and ASTM C1293) on the ASR potential of construction aggregates. The results of these tests were compared with the results of a more accelerated test (ASTM C441) that uses an extremely reactive synthetic ag...
Vibrational Raman spectra of micro-droplets and micro-crystals of nitrogen formed in free jet expansions

Abstract Stimulated Raman loss spectroscopy (SRLS) has been used in a study of very large aggregates of N 2 (estimated 10 6 –10 9 molecules) produced by expansion from a channel nozzle. By probing at different distances from the nozzle opening, well-defined frequency shifts are observed which characterize gas-liquid, liquid-solid, and β- to α-solid phase transitions. The internal temperature of the aggregates, the rotational temperature of the monomer, and the approximate monomer/aggregates ratio were also determined. This is the first application of non-linear Raman techniques to the observation of phase transitions in jet expansions.
Toward Correct Protein Folding Potentials

Empirical protein folding potential functions should have a global minimum near the nat- ive conformation of globular proteins that fold stably, and they should give the correct free energy of folding. We demonstrate that otherwise very successful potentials fail to have even a local minimum anywhere near the native conformation, and a seemingly well validated method of estimating the thermodynamic stability of the native state is extremely sensitive to small perturbations in atomic coordinates. These are both indicative of fitting a great deal of irrelevant detail. Here we show how to devise a robust potential function that succeeds very well at both tasks, at least for a limited set of proteins, and this involves developing a novel representation of the denatured state. Predicted free energies of unfolding for 25 mutants of barnase are in close agreement with the experimental values, while for 17 mutants there are substantial discrepancies.
Solar flare intermittency and the earth's temperature anomalies.

We argue that Earth's short-term temperature anomalies and the solar flare intermittency are linked. The analysis is based upon the study of the scaling of both the spreading and the entropy of the diffusion generated by the fluctuations of the temperature time series. The joint use of these two methods evidences the presence of a Levy component in the temporal persistence of the temperature data sets that corresponds to the one that would be induced by the solar flare intermittency. The mean monthly temperature data sets cover the period from 1856 to 2002.
On p-adic zeros of forms

Abstract Using the procedure of G. I. Arkhipov and A. A. Karatsuba (Math. USSR-Izv. 19 (1982), 321–340), their exponential lower bound on the number of variables possible for a form of degree d having only the trivial p-adic zero is sharpened.
Bayesian Unsupervised Topic Segmentation

This paper describes a novel Bayesian approach to unsupervised topic segmentation. Unsupervised systems for this task are driven by lexical cohesion: the tendency of well-formed segments to induce a compact and consistent lexical distribution. We show that lexical cohesion can be placed in a Bayesian context by modeling the words in each topic segment as draws from a multinomial language model associated with the segment; maximizing the observation likelihood in such a model yields a lexically-cohesive segmentation. This contrasts with previous approaches, which relied on hand-crafted cohesion metrics. The Bayesian framework provides a principled way to incorporate additional features such as cue phrases, a powerful indicator of discourse structure that has not been previously used in unsupervised segmentation systems. Our model yields consistent improvements over an array of state-of-the-art systems on both text and speech datasets. We also show that both an entropy-based analysis and a well-known previous technique can be derived as special cases of the Bayesian framework.
Ernst Mayr: Biologist-historian

Ernst Mayr's historical writings began in 1935 with his essay “Bernard Altum and the territory theory” and have continued up through his monumentalGrowth of Biological Thought (1982) and hisOne Long Argument: Charles Darwin and the Genesis of Modern Evolutionary Thought (1991). Sweeping in their scope, forceful in their interpretation, enlisted on behalf of the clarification of modern concepts and of a broad view of biology, these writings provide both insights and challenges for the historian of biology. Mayr's general intellectual formation was guided by the GermanBildung ideal, with its emphasis on synthetic and comprehensive knowledge. His understanding of how to write history was inspired further by the example of the historian of ideas Arthur Lovejoy. Some strengths and limitations of this approach are explored here through attention to Mayr's treatment of the French biologist J.-B. Lamarck. It is contended that Mayr's contributions to the history of biology are not restricted to his own very substantial historical writings but also include his encouragement of other scholars, his development of an invaluable archive of scientific correspondence, and his insistence that historians who write about evolution and related subjects acquire an adequate understanding of the principles of Darwinian biology.