cssi/SciSciGPT-SciSciNet huggingface dataset:
AnchorViz: Facilitating Semantic Data Exploration and Concept Discovery for Interactive Machine Learning

When building a classifier in interactive machine learning (iML), human knowledge about the target class can be a powerful reference to make the classifier robust to unseen items. The main challenge lies in finding unlabeled items that can either help discover or refine concepts for which the current classifier has no corresponding features (i.e., it has feature blindness). Yet it is unrealistic to ask humans to come up with an exhaustive list of items, especially for rare concepts that are hard to recall. This article presents AnchorViz, an interactive visualization that facilitates the discovery of prediction errors and previously unseen concepts through human-driven semantic data exploration. By creating example-based or dictionary-based anchors representing concepts, users create a topology that (a) spreads data based on their similarity to the concepts and (b) surfaces the prediction and label inconsistencies between data points that are semantically related. Once such inconsistencies and errors are discovered, users can encode the new information as labels or features and interact with the retrained classifier to validate their actions in an iterative loop. We evaluated AnchorViz through two user studies. Our results show that AnchorViz helps users discover more prediction errors than stratified random and uncertainty sampling methods. Furthermore, during the beginning stages of a training task, an iML tool with AnchorViz can help users build classifiers comparable to the ones built with the same tool with uncertainty sampling and keyword search, but with fewer labels and more generalizable features. We discuss exploration strategies observed during the two studies and how AnchorViz supports discovering, labeling, and refining of concepts through a sensemaking loop.
Teaching NeuroImages: Cranial neuropathies following clival infarction.

An 18-year-old man with hemoglobin SS-type sickle cell disease presented with acute onset of headaches and horizontal double vision. On examination, he was noted to have a right cranial nerve VI (abducens) palsy. The following day, he also developed an ipsilateral cranial nerve VII (facial) palsy. Neuroimaging was consistent with bony infarction of his clivus secondary to his sickle cell disease and inflammation of the adjacent dura (figure). His presentation and imaging findings are suggestive of transient inflammation of cranial nerves VI and VII as they passed in proximity to the peri-infarct inflammation along the skull base. He received apheresis for elevated sickle hemoglobin levels, and his symptoms resolved within 1 week. His repeat imaging showed resolution of the areas of inflammation and evolution of his bony infarct. His most recent evaluation by neurology at 2 years follow-up was unremarkable, and his symptoms have not recurred.
Assessment of Shave Removal Without Further Excision in the Treatment of Spitz Nevi: A Retrospective Study of 58 Cases:

BackgroundSpitz nevi (or tumors) are noncancerous growths that are found particularly in the pediatric population. Their histologic features overlap with melanoma, but they have a favorable prognos...
Association Between Sexual Orientation and Lifetime Prevalence of Skin Cancer in the United States

Importance Sexual minority men have reported higher rates of both indoor tanning and skin cancer than heterosexual men, and sexual minority women have reported lower or equal rates of both indoor tanning and skin cancer compared with heterosexual women. Bisexual men, in particular, have reported higher rates of indoor tanning bed use than heterosexual men; however, no study has investigated skin cancer prevalence among gay, lesbian, and bisexual individuals as separate groups. Objective To evaluate the association between sexual orientation and lifetime prevalence of skin cancer. Design, Setting, and Participants This cross-sectional study analyzed data from the 2014-2018 Behavioral Risk Factor Surveillance System (BRFSS) surveys of a noninstitutionalized population in the United States that included 877 650 adult participants who self-identified as being heterosexual, gay, lesbian, or bisexual. Main Outcomes and Measures Self-reported lifetime history of skin cancer. Results The study included 877 650 participants, including 364 833 heterosexual men (mean age, 47.7; 95% CI, 47.5-47.8), 7823 gay men (mean age, 42.7; 95% CI, 41.8-43.6), 5277 bisexual men (mean age, 39.4; 95% CI, 38.4-40.5), 484 341 heterosexual women (mean age, 49.7; 95% CI, 49.6-49.8), 5609 lesbian women (mean age, 41.8; 95% CI, 40.6-43.0), and 9767 bisexual women (mean age, 32.8; 95% CI, 32.3-33.3). The adjusted odds ratios (AORs) of skin cancer prevalence were significantly higher among both gay (AOR, 1.25; 95% CI, 1.03-1.50;P = .02) and bisexual men (AOR, 1.46; 95% CI, 1.01-2.10;P = .04) compared with heterosexual men. The AORs of skin cancer were statistically significantly lower among bisexual women (AOR, 0.75; 95% CI, 0.60-0.95;P = .02) but not among gay or lesbian women (AOR, 1.01; 95% CI, 0.77-1.33;P = .95) compared with the AORs of skin cancer among heterosexual women. Conclusions and Relevance In this study, gay and bisexual men had an increased self-reported lifetime prevalence of skin cancer compared with the prevalence among heterosexual men. Patient education and community outreach initiatives focused on reducing skin cancer risk behaviors among gay and bisexual men may help reduce the lifetime development of skin cancer in this population. Continued implementation of the Behavioral Risk Factor Surveillance System’s sexual orientation and gender identity module is imperative to improve understanding of the health and well-being of sexual minority populations.
Implementation of Soil Moisture Sensor Based Automated Irrigation in Woody Ornamental Production1

Abstract A soil moisture sensor-based automated irrigation system was trialed in a commercial ornamental nursery over the 2014-2015 growing seasons. In both years, use of the sensor-based system re...
Combat Lessons Learned

Lessons learned during military conflicts caring for victims of combat injury have translated to advancements in the care of civilian patients for millennia. The most recent worldwide conflict is no exception, and surgical care specifically has seen some of the greatest evolution. Prior dogma has been examined and debunked in several instances, surgical care paradigms once relegated to history have been resurrected, and modern civilian trauma systems have been applied in combat environments for the first time which have then yielded new knowledge to further improve care for injured patients back in the civilian setting.
Abstract 5679: Androgen receptor degraders overcome common resistance mechanisms developed during prostate cancer treatment

Background: Androgen receptor (AR) signaling is critical for prostate development and homeostasis as well as for the initiation and progression of prostate cancer (PCa). Indeed, the clinical development of second-generation AR antagonists, including enzalutamide, has confirmed that AR remains a key oncogene in castration-resistant prostate cancer (CRPC). Furthermore, response to enzalutamide is temporary and incremental, and PCa cells that develop resistance to AR-targeted therapy usually maintain AR expression. Therefore, with the hypothesis that AR protein is still active even during castration- and enzalutamide-resistant states, we employed the proteolysis targeting chimera (PROTAC) strategy to build compounds that targeted the AR through proteasomal degradation. We developed an optimized functional molecule, ARD-61, that targets enzalutamide-resistant and AR splice variant (including AR-V7, which lacks the ligand binding domain) overexpressing cells in vitro and in vivo. Methods/Results: To characterize ARD-61, we performed western blotting, qRT-PCR, growth assays, xenograft studies, as well as proteomic and RNA-sequencing analyses. Additionally, to investigate the sensitivity of AR splice variants to ARD-61, we created CRISPR-Cas9 mediated stable AR-V7 overexpression in LNCaP cells. ARD-61 functions to rapidly and specifically degrade AR protein, and thus decreases downstream AR signaling in a wide variety (e.g. enzalutamide sensitive, AR-mutated, enzalutamide resistant) of AR-positive cell lines and tumor xenografts. Enzalutamide-sensitive and -resistant cell lines were similarly sensitive to ARD-61 in vivo and in vitro. CRISPR-induced endogenous overexpression of AR-V7 had no effect on the sensitivity of cells to ARD-61 or enzalutamide. Conclusions: Our data reveal the necessity of full-length AR in all Pca stages. Despite continued AR-antagonization, enzalutamide-resistant cell lines require full-length AR for sustained survival. Further, AR-variant overexpression, previously shown to promote resistance to AR-targeted therapies, still required AR protein with an intact ligand-binding domain to maintain growth in our models. Our data illustrate the importance of continued targeting of AR in advanced Pca, as well as demonstrate the efficacy of ARD-61. Ultimately, through its clinical translation, we anticipate the development of ARD-61 to be a therapeutic advance for patients with the metastatic CRPC. Citation Format: Steven Kregel, Chao Wang, Xin Han, Lanbo Xiao, Ester Fernandez-Salas, Pushpinder Bawa, Brooke L. McCollum, Kari Wilder-Romans, Ingrid J. Apel, Xuhong Cao, Corey Speers, Shaomeng Wang, Arul M. Chinnaiyan. Androgen receptor degraders overcome common resistance mechanisms developed during prostate cancer treatment [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 5679.
Vascular endothelial mitochondrial oxidative stress in response to preeclampsia: a role for angiotension II type 1 autoantibodies

Background Preeclampsia is characterized by a new onset of hypertension during pregnancy and is associated with autoantibodies against the angiotensin II type 1 receptor and oxidative stress. There is growing evidence for mitochondrial dysfunction in preeclampsia, however, the culprits for mitochondrial dysfunction are still being defined. We previously demonstrated that angiotensin II type 1 autoantibodies cause renal, placental, and endothelial mitochondrial dysfunction in pregnant rats. However, the role of the angiotensin II type 1 autoantibodies in endothelial mitochondrial function in response to sera from preeclamptics is unknown. Thus, we hypothesized that circulating factors, such as the angiotensin II type 1 autoantibodies, during preeclampsia would negatively impact the vascular endothelial mitochondrial function in human umbilical vein endothelial cells. Objective The objective of the study was to determine a role for circulating angiotensin II type 1 autoantibodies to cause endothelial mitochondrial reactive oxygen species and dysfunction in preeclampsia compared to normal pregnant controls. Study Design Immediately after delivery, sera was collected from preeclamptic patients and normal pregnant controls. The mitochondrial reactive oxygen species were determined from the cells treated overnight with 10% sera from either the control or preeclamptic patients with and without the antiotension II type 1 autoantibodies inhibitor peptide (‘n7AAc’). Results Preeclampsia patients at Conclusion This study demonstrates that endothelial mitochondrial dysfunction occurs in response to circulating factors, especially in response to serum from preterm preeclampsia patients, and can be restored by blocking circulating angiotensin II type 1 autoantibodies, thereby indicating a potential new therapeutic target for preeclampsia.
Smart City Innovations to Improve Quality of Life in Urban Settings

While definitions of a Smart City vary, they unequivocally emphasize improvement in the quality of life for citizens through approaches such as improved mobility and transportation systems, a more resilient built environment, or identifying and mitigating various kinds and sources of pollution. Ultimately, the characteristics of a Smart City are defined by its innovations. Motivated by the exponential growth in the number of large cities as well as their populations, municipal and regional governments worldwide have begun to implement smart innovations to manage everyday activities more efficiently. Smart city innovations range in scope, some more technological or data-oriented than others, but for all, the main goal is to effectively meet the evolving needs of its citizens. This paper discusses contemporary issues faced by cities, specifically those related to urban mobility and transportation, urban air pollution, quality of life, and accessibility for short-term visitors. Context-appropriate innovations that have successfully addressed some of these issues in different world regions are described with the overarching objective of inspiring and informing the next generation of smart city innovations.
Civil Rights Act of 1866: Salvaging Equal Rights Under the Law for the Contemporary Minority Small Business Owner

The Civil Rights Act of 1866 (42 U.S.C. § 1981) protects against racial discrimination in the making and enforcement of contracts. Section 1981 provides that all people have the same right to make and enforce contracts as is enjoyed by white citizens. Plaintiffs bringing a Section 1981 claim can recover not only compensatory damages for a breached contract, but also tort-like remedies, such as punitive and emotional distress damages, normally denied to a plaintiff in a breach of contract case. Minority-owned businesses are among the parties that have sought relief under Section 1981; however, when the business is the contracting party, courts have held that some business owners and corporate shareholders lack standing under the statute despite evidence of racial discrimination and substantial liabilities incurred by business owners. Consequently, courts have denied remedies for compensatory damages, such as emotional distress, to the very parties that Section 1981 seeks to protect. In some cases, courts have used the common law contracts doctrine of third-party beneficiaries to give relief to injured parties not in privity of contract. However, the application of this doctrine is far from uniform. This Note proposes an amendment to the Section 1981 statute to incorporate a tortious interference test and a third-party beneficiary test, which will allow recovery for the economic injuries to business owners and shareholders of businesses seeking relief under Section 1981.
Mortality among people who inject drugs: a prospective cohort followed over three decades in Baltimore, MD, USA.

Background and aims Over the past decades, people who inject drugs (PWID) have been impacted by the development of combination antiretroviral therapy (cART) to combat HIV/AIDS, the prescription opioid crisis, and increased use of lethal synthetic opioids. We measured how these dynamics have impacted mortality among PWID in an urban U.S. city. Design Prospective cohort study using data from the AIDS Linked to the Intravenous Experience (ALIVE) SETTING: Baltimore, Maryland, USA from 1988-2018. Participants 5,506 adult PWIDs (median age at baseline 37 years). Measurements Mortality was identified by linkage to National Death Index-Plus (NDI-Plus) and categorized into HIV/infectious disease (HIV/ID) deaths, overdose and violence-related (drug-related) deaths, and chronic-disease deaths. Person-time at risk accrued from baseline, and ended at the earliest of death or study period. All-cause and cause-specific mortality were calculated annually. Fine and Gray method was used to estimate the sub-distribution hazards of cause-specific deaths accounting for competing risks. Findings Among 5,506 participants with 84,011 person-years of follow-up, 43.9% were deceased by 2018. Among all deaths, 30.5% were HIV/ID-deaths, 24.4% drug-related deaths, and 33.3% chronic-disease deaths. Age-standardized all-cause mortality increased from 23 to 45 per 1000-person-years from 1988-1996, declined from 1996 through 2012, then trended upward through 2018. HIV/ID-deaths peaked in 1996 coincident with the availability of cART, then continuously declined. Chronic-disease deaths increased continuously as the cohort aged. Drug-related deaths declined until 2011, but increased over 4-fold by 2018. HIV/HCV infection and active injecting were independently associated with HIV/ID and drug-related deaths. Female and Black participants had higher risk of dying from HIV/ID deaths and a lower risk of dying from drug-related deaths than male and non-Black participants. Conclusions Deaths in Baltimore, Maryland, USA attributable to HIV/ID appear to have declined following the widespread use of combination antiretroviral therapy. Increases in the rates of drug-related deaths in Baltimore were observed prior to and continue in conjunction with national mortality rates associated with the opiate crisis.
Delivery of siRNA via cationic Sterosomes to enhance osteogenic differentiation of mesenchymal stem cells

Noggin is a specific antagonist of bone morphogenetic proteins (BMPs) that can prevent the interaction of BMPs with their receptors. RNA interfering molecules have been used to downregulate noggin expression and thereby stimulate BMP signaling and osteogenesis. Cationic liposomes are considered one of the most efficient non-viral systems for gene delivery. In the past decade, non-phospholipid liposomes (Sterosomes) formulated with single-chain amphiphiles and high content of sterols have been developed. In particular, Sterosomes composed of stearylamine (SA) and cholesterol (Chol) display distinct properties compared with traditional phospholipid liposomes, including increased positive surface charges and enhanced particle stability. Herein, we report SA/Chol Sterosome and small interfering RNA (siRNA) complexes that significantly enhanced cellular uptake and gene knockdown efficiencies in adipose derived mesenchymal stem cells with minimal cytotoxicity compared with commercially available lipofectamine 2000. Furthermore, we confirmed osteogenic efficacy of these Sterosomes loaded with noggin siRNA in in vitro two- and three-dimensional settings as well as in a mouse calvarial defect model. The delivery of siRNA via novel SA/Chol Sterosomes presents a powerful method for efficient gene knockdown. These distinct nanoparticles may present a promising alternative approach for gene delivery.
Constituency Representation in Congress: The Psychology of Constituency Representation

Legislative perceptions of constituents are a fundamental component of political representation because legislators represent the district they see. In order to understand legislative behavior, therefore, it is essential to see the constituency through the eyes of the legislative enterprise. Despite the early consensus on the importance of legislative perceptions (e.g., Dexter 1957; Fenno 1978; Kingdon 1967; Miller and Stokes 1963), political scientists' understanding of how perception affects congressional representation has been limited by the lack of a theory of perception. With no explicit model of the process by which legislative perceptions of the district are formed, questions about which subconstituencies are more or less likely to be perceived by legislative offices – and the impact of these patterns on congressional representation – remain unanswered. Two important developments offer new insights into the cognitive processes that shape how legislators perceive the constituents in their district. The first of these developments is the growth of research on social cognition in the psychology literature, particularly individuals' use of heuristics, or mental shortcuts, to simplify complex environments. The cognitive psychology literature offers an information-based approach to individuals' perceptions of the world around them that emphasizes how individuals use information, including their reliance on the accessibility heuristic. The second, related, development is the growth of political psychology within the political science discipline, especially research on citizens' use of information in political judgments.
Effects of the interrelationship between zinc oxide and copper sulfate on growth performance of early-weaned pigs

We conducted four experiments to examine the effects of adding zinc oxide (ZnO) and(or) copper sulfate (CuSO4) to diets for weanling pigs. In Exp. 1 and 2, weanling pigs (initially 5.3 kg and 19 +/- 2 d of age) were fed diets containing 250 ppm of added Cu (CuSO4) and either 110 or 3,110 ppm of added. Zn (ZnO). No differences (P > .10) were observed in either experiment for ADG, ADFI, or feed efficiency (G:F). In Exp. 3,240 pigs (initially 4.45 kg and 15 +/- 2 d of age) were used to determine the interactive effects of added dietary ZnO and(or) CuSO4. Dietary treatments were in a 2 x 2 factorial arrangement; Zn (165 or 3,000 ppm) and Cu (16.5 or 250 ppm) were the main effects. Pigs were fed a high nutrient dense diet from d 0 to 14 after weaning and a less complex diet from d 14 to 28 after weaning, both containing the same mineral fortifications. From d 0 to 14, pigs fed 3,000 ppm Zn, with or without 250 ppm Cu, had improved ADG (P < .01) compared with pigs fed the control (16.5 ppm Cu and 165 ppm Zn) or diets with only added Cu. From d 14 to 28, pigs fed the diet containing 3,000 ppm added Zn, without 250 ppm Cu, had greater ADG than pigs fed the other diets (Zn x Cu interaction, P < .01). In Exp. 4, 264 pigs (initially 4.17 kg and 12 +/- 3 d of age) were fed a high nutrient dense diet supplemented with 3,000 ppm of Zn (ZnO) from d 0 to 14 after weaning. On d 14, pigs were switched to the diets containing experimental mineral levels identical to those of Exp. 3. From d 14 to 28 after weaning, added Zn improved ADG but not when the diet contained 250 ppm Cu (Zn x Cu interaction, P < .05). Feeding 3,000 ppm of Zn from ZnO is a viable means of improving nursery pig performance, but additive responses to growth-promotant levels of CuSO4 (250 ppm Cu) were not observed.
Characterization of T7-specific Ribonucleic Acid Polymerase IV. RESOLUTION OF THE MAJOR IN VITRO TRANSCRIPTS BY GEL ELECTROPHORESIS

Abstract The major in vitro RNA transcripts synthesized by T7 RNA polymerase with T7 and T3 DNA templates have been resolved by electrophoresis on polyacrylamide gels. Six discrete size classes of T7 RNAs are found, designated I to VI. The apparent molecular weights, estimated from their electrophoretic mobilities, span a broad range, from 2 x 105 to 5 x 106. At least two minor RNA species, with molecular weights greater than 5 x 106, are also detected. The six major T7 RNA species are synthesized in approximately equimolar amounts, with the exception of species III, which is made in about twice this amount. It is likely that species III is a mixture of two RNAs ("IIIa" and "IIIb") transcribed from separate regions of the T7 genome. Hence, the six major T7 RNA species are tentatively identified with seven late transcription units on the phage chromosome, which are read with equal efficiences. The six (or seven) transcription products are initiated independently with guanosine triphosphate at the 5' terminus, and are elongated at a rate of 230 nucleotides per s under standard in vitro conditions. When T7 RNA polymerase is used to transcribe T3 DNA, a single RNA transcript is found, with a molecular weight similar to that of T7 RNA species III. This suggests an explanation for the reduced rate of T3 RNA synthesis by T7 RNA polymerase in vitro, and implies that T3 promoter sites read by the T3 RNA polymerase are heterogeneous in nature.
Primary U distribution in scleractinian corals and its implications for U series dating

In this study we use microsampling techniques to explore diagenetic processes in carbonates. These processes are important as they can affect the accuracy of U series chronometry. Fission track maps of deep-sea scleractinian corals show a threefold difference between the minimum and maximum [U] in modern corals, which is reduced to a factor of 2 in fossil corals. We use micromilling and MC-ICP-MS to make detailed analyses of the [U] and δ234Uinitial distributions in corals from 218 ka to modern. Within each fossil coral we observe a large range of δ234Uinitial values, with high δ234Uinitial values typically associated with low [U]. A simple model shows that this observation is best explained by preferential movement of alpha-decay produced 234U atoms (alpha-recoil diffusion). Open-system addition of 234U may occur when alpha-recoil diffusion is coupled with a high [U] surface layer, such as organic material. This process can result in large, whole-coral δ234Uinitial elevations with little effect on the final age. The diagenetic pathways that we model are relevant to both shallow-water and deep-sea scleractinian corals since both exhibit primary [U] heterogeneity and may be subject to U addition.
Microlymphatics and lymph flow

A careful review of several different organs shows that with the information available today the beginnings of the microlymphatics in the tissue consist of endothelialized tubes only. Lymphatic smooth muscle within the collecting lymphatics appears further downstream, in some organs only outside the parenchyma. This particular anatomic picture has been observed in many different mammalian organs and in humans. The nonmuscular, so-called initial, lymphatics are the site of interstitial fluid absorption that requires only small and transient pressure gradients from the interstitium into the initial lymphatics. A fundamental question concerns the mechanism that causes expansion and compression of the initial lymphatics. I presented several realistic proposals based on information currently on hand relevant to the tissue surrounding the initial lymphatics. To achieve a continuous lymphatic output, periodic (time variant) tissue stresses need to be applied. They include arterial pressure pulsations; arteriolar vasomotion; intestinal smooth muscle contractions and motilities; skeletal muscle contraction; skin tension; and external compression, such as during walking, running, or massage, respiration, bronchiole constriction, periodic tension in tendon, contraction and relaxation of the diaphragm, tension in the pleural space during respiration, and contractions of the heart. The nonmuscular initial lymphatic system drains into a set of contractile collecting lymphatics, which by way of intrinsic smooth muscle propel lymph fluid. The exact transition between noncontractile and contractile lymphatics has been established only in a limited number of organs and requires further exploration. Retrograde flow of lymph fluid is prevented by valves. There are the usual macroscopic bileaflet valves in the initial and collecting lymphatics and also microscopic lymphatic endothelial valves on the wall of the initial lymphatics. The latter appear to prevent convective reflow into the interstitium during lymphatic compression. Many of the lymph pump mechanisms have been proposed in the past, and most authors agree that these mechanisms influence lymph flow. However, the decisive experiments have not been carried out to establish to what degree these mechanisms are sufficient to explain lymph flow rates in vivo. Because individual organs have different extrinsic pumps at the level of the initial lymphatics, future experiments need to be designed such that each pump mechanism is examined individually so as to make it possible to evaluate the additive effect on the resultant whole organ lymph flow.(ABSTRACT TRUNCATED AT 400 WORDS)
Complete hyperbolicity in Hamiltonian systems with linear potential and elastic collisions

Abstract We present a class of systems with all Lyapunov exponents different from zero (completely hyperbolic). They are obtained by the restriction of the configuration space of a simple completely integrable system with linear potential and elastic collisions. We show that special geometry of the configuration space is necessary. We survey concrete realizations of this scheme discussed previously in [16] and elsewhere.
Reaction rates for 8Li(p, α) and 8Li(p, n, α) and their effect on primordial nucleosynthesis

Abstract Differential-cross-section data are presented for the 8 Li(p, α) 5 He reaction at 1.5 MeV center-of-mass energy, measured with a (radioactive) 8 Li beam. The data are used to calculate one of the terms of the thermonuclear reaction rate for destruction of 8 Li. In addition, other data are used to estimate the total reaction rate for p+ 8 Li, which is found to be comparable to that used in previous calculations of abundances from primordial nucleosynthesis.
Influence of streptozotocin-induced diabetes on adenylate cyclase activity in cultured type II pneumocytes.

Previous studies with cultured type II pneumocytes from streptozotocin-induced diabetic rats demonstrated altered surfactant synthesis and secretion. The effects of the diabetic state were reversed by in vivo but not in vitro insulin treatment. In the current study, cultured type II pneumocytes from control and streptozotocin-induced diabetic rats were demonstrated to possess approximately 17,500 and 8,500 receptors per cell, respectively. High-affinity binding sites were determined to have a dissociation constant of 0.429 nM and 0.203 nM for control and diabetic cells, respectively. Functional capacity of the insulin receptors was determined by the initial rates of 2-deoxy-d-glucose uptake. Uptake was stimulated by insulin in a dose-dependent manner and was not significantly altered by the diabetic state. This would suggest that the insulin receptor was present and functioning in cells isolated from diabetic rats. Basal adenylate cyclase activity of type II cell homogenates from diabetic rats was shown t...
The cost-effectiveness of prize-based and voucher-based contingency management in a population of cocaine- or opioid-dependent outpatients.

Objective To evaluate the cost-effectiveness of using prize-based and voucher-based contingency management (CM) as additions to standard treatment for cocaine- or heroin-dependent outpatients in community treatment centers.
ErbB4 regulation of a thalamic reticular nucleus circuit for sensory selection

The authors show that mice lacking the gene Erbb4 in somatostatin-expressing (SOM) neurons of the thalamic reticular nucleus (TRN) show selective behavioral deficits in tasks involving switching attention between cues of different sensory modalities. Slice recordings also showed enhanced cortical drive in Erbb4-deficient TRN SOM neurons.
Physiological and pathological functions of acid-sensing ion channels in the central nervous system

Protons are important signals for neuronal function. In the central nervous system (CNS), proton concentrations change locally when synaptic vesicles release their acidic contents into the synaptic cleft, and globally in ischemia, seizures, traumatic brain injury, and other neurological disorders due to lactic acid accumulation. The finding that protons gate a distinct family of ion channels, the acid-sensing ion channels (ASICs), has shed new light on the mechanism of acid signaling and acidosis-associated neuronal injury. Accumulating evidence has suggested that ASICs play important roles in physiological processes such as synaptic plasticity, learning/memory, fear conditioning, and retinal integrity, and in pathological conditions such as brain ischemia, multiple sclerosis, epileptic seizures, and malignant glioma. Thus, targeting these channels may lead to novel therapeutic interventions for neurological disorders. The goal of this review is to provide an update on recent advances in our understanding of the functions of ASICs in the CNS.
Pathophysiology corner: Inflammation I

It is now 9:20 am and BB, your first case, arrives in the PACU. You receive the following report from the nurse anesthetist: a 42-year-old man with a negative past medical history and no allergies, who had a 70-minute case for an attempted laparoscopic, and then an open appendectomy. The appendix was found to be ruptured with approximately a 10-cm abscess that was drained and copiously irrigated. BB had an unremarkable anesthetic course, with a rapid sequence induction with 200 mg of propofol, 2 cc of fentanyl, 2 mg of midazolam, and succinylcholine for induction, and then sufentanil and vecuronium for maintenance. Five milligrams of morphine was titrated in at the end of the case, and he was reversed and extubated without incident. BB received 1,300 cc of lactated ringers (LR), with an estimated blood loss (EBL) of 50 cc and no urinary catheter. He was noted to have an episodic drop in blood pressure on induction, which was rapidly corrected with IV fluids. BB’s PACU admission VS: Temp. 100.7°F (Tympanic), BP 112/70, HR 114, RR 24, and an oxygen saturation of 98% on 3 LPM O2.
Azathioprine effect on normal canine liver and kidney function.

Abstract Unrelated adult mongrel dogs, without transplantation, were administered a pharmacologic dose of azathioprine (1–4 mg/kg/day orally) and antibiotics for 180 days. Blood was drawn and urine was collected biweekly for the following analysis: (1) lipid profile; total lipids, triglyceride, cholesterol (total, free, and ester), phospholipid, and nonesterified fatty acids; (2) kidney function; urine and plasma milliosmoles, potassium, sodium, and chlorides; (3) liver function; alkaline phosphatase, serum glutamic-oxaloacetic transaminase, bilirubin, fibrinogen, and blood sugar; (4) hematology; hematocrit and white blood cell count. All dogs retained their original body weight. Plasma phospholipids increased, but no significant changes occurred in the other blood lipids. The white blood cell count was reduced 50% or more in 5–10 days. Hematocrit dropped 10–20% from predose levels in 15–20 days. The blood enzymes increased as much as twentyfold beginning 2–10 days after drug administration in all but one of the dogs. The urinary and plasma electrolytes fluctuated in a normal range. Plasma sugar, bilirubin, and fibrinogen were not affected by this immunosuppressive regimen. Three successive “high” levels of azathioprine (4 mg/kg/day, orally) produced a similar response delay (2–7 days) and a similar quantitative result. The azathioprine regimen did not produce a repeated “rejection cycle” when continuously administered.
Evaluation of putative hazard tests under background risk heterogeneity

In this paper, an evaluation of some tests for adverse health effects around fixed locations (putative hazard sites) is made. We address the situation where a heterogeneous background is included both in terms of correlated and uncorrelated heterogeneity (UH). In addition, we examine a set of tests for case event data (residential case addresses) including both distance and directional effects. The tests include distance and directional score tests (DIR), integrated intensity tests, the Besag & Newell (BES) test, and Kulldorff's focus clustering scan test. Monte Carlo power of the tests is evaluated and power curves are finally presented. Interesting results from this work include the lack of power found when correlated heterogeneity (CH) is present. This is not found with UH. The BES and Scan tests have lower power than the integrated intensity tests and score tests in general. The integrated intensity test demonstrates its omnibus ability to detect either distance or directional effects. Copyright © 2008 John Wiley & Sons, Ltd.
Role of the Mitochondrion in Programmed Necrosis

In contrast to the “programmed” nature of apoptosis and autophagy, necrotic cell death has always been believed to be a random, uncontrolled process that leads to the “accidental” death of the cell. This dogma, however, is being challenged and the concept of necrosis also being “programmed” is gaining ground. In particular, mitochondria appear to play a pivotal role in the mediation of programmed necrosis. The purpose of this review, therefore, is to appraise the current concepts regarding the signaling mechanisms of programmed necrosis, with specific attention to the contribution of mitochondria to this process.
Diffusion of Iron, Cobalt, and Nickel in Single Crystals of Pure Copper

The rates of diffusion of radioactive tracers of Fe, Co, and Ni in single crystals of pure copper have been measured as a function of temperature from about 700 to 1075 deg C. The results, obtained by the tracer-sectioning technique, are as follows: D/sub Fe yields Cu/ = 1.4 exp(-51,800/RT); D/sub Co yields Cu/ = 193 exp(--54,100/RT); D/sub Ni yields Cu/ = 2.7 exp(--56,500/RT); all in units of cm/sup 2/sec. An exploratory measurement for a Mn tracer in copper was made at 1069 deg C with the result D = 1.49 x 10/sup -8/ cm/sup 2/sec. The results of several current theoretical calculations are compared with the present data: Wert and Zener's correlation of D/sub O/ and Q is supported by the present work; the basic qualitative prediction of Lazarus' screening theory is borne out by the present results, although the extent of the detailed agreement is not clear at this time. The experimental data yielded unexpectedly large diffusion coefficients at low temperatures in some cases and several possible causes are considered. Finally, a new experimentel method is described for determining diffusion coefficients with tracers emitting only very low--energy particles. (auth)
Sperm surface components involved in the control of the acrosome reaction

Several lines of evidence suggest that decapacitation of sperm occurs normally in the male reproductive tract, and as a result the acrosome is stabilized and the acrosome reaction is controlled. Since the defining experiments in 1951, where decapacitation was reversed in the female reproductive tract by capacitation, investigations have pursued the molecular events of this process. This review attempts to examine critically the older literature and compare that perspective with the current theories. The theories for decapacitation of sperm include the possible role of a peptide decapacitation factor, a glycoprotein-mediated steroid transfer to the sperm, masking of a galactosyl transferase by some macromolecule-containing carbohydrate, preclusion of calcium influx by a binding protein, and sperm interaction with the acrosome stabilizing factor. Although these theories are diverse, there are some unifying aspects. However, there remain some major unanswered questions. For example, although we point to some circumstantial evidence that infers a single decapacitation factor, this needs to be further substantiated. It is concluded that with the purification of a macromolecule involved in capacitation, specific proposals on the mechanism of capacitation, and new tools to evaluate the capacitation process, it is likely that another decade will not pass without emergence of a unifying molecular theory of sperm capacitation.
Infection in Renal Transplant Recipients

Renal transplant recipients are susceptible to infection by a wide array of pathogens. Impaired inflammatory responses due to immunosuppressive therapies suppress clinical and radiologic findings engendered by microbial invasion. As a result, patients are often minimally symptomatic and evaluation and diagnosis are delayed. Specific microbiologic diagnosis is essential both for the optimization of antimicrobial therapy and to avoid unnecessary drug toxicities. Differential diagnosis is guided by knowledge of organisms commonly involved in infection in immunocompromised hosts and understanding of the limitations of prophylactic strategies. The risk of infection in the organ transplant recipient is determined by the interaction between the individual's epidemiologic exposures and net state of immunosuppression. Epidemiology includes environmental exposures in the community and hospital, organisms derived from donor tissues and latent infections activated in the host during immune suppression. The net state of immune suppression is determined by the interaction of all factors contributing to infectious risk. Routine antimicrobial prophylaxis is aimed at common infections and unique risk factors in individual patient groups. This includes trimethoprim-sulfamethoxazole (for Pneumocystis, Toxoplasma, most Nocardia and Listeria, common urinary pathogens), perioperative (eg, anti-fungal prophylaxis for pancreas transplants), or antiviral (for herpesviruses in high risk recipients).
Histochemical mapping of succinic dehydrogenase and cytochrome oxidase in the diencephalon and basal telencephalic centers of the brain of squirrel monkey (Saimiri sciureus).

The distribution of succinic dehydrogenase (SDA) and cytochrome oxidase (Cy. O) was mapped in the various diencephalic nuclei and basal telencephalic centers of the squirrel monkey brain. Thirty μ thick formaldehyde fixed serial sections were also studied for the delineation of the various nuclei, but histochemical preparations proved equally useful for this purpose. Strong SDA and Cy. O activity were observed in the habenular, pulvinaris, anterior dorsalis and ventralis, lateralis dorsalis and posterior, and ventral posterior nuclei. The corpus geniculatum laterale and mediale also showed a strong reaction for these enzymes. The nucleus ventralis anterior, which occupies a very large area in the rostral part of the thalamus, showed moderately strong activity in the cellular patches and negligible activity in the thick fiber bundles passing through it. A comparatively weak reaction was observed in the midline thalamic nuclei. The nucleus caudatus and putamen, however, showed very strong SDA/Cy. O activity. The hypothalamic nuclei showed mild Cy. O and moderate SDA reactions, except for the nucleus ventromedialis hypothalami. The latter showed a little stronger enzyme reaction. The fibers of the internal capsule and the anterior commissure showed little SDA and mild Cy. O activity. The various nuclei of the amygdaloid complex showed similar histochemical reactions with moderate SDA and mild Cy. O activity.
Cadmium and the laying hen: apparent absorption, tissue distribution and virtual absence of transfer into eggs.

After being given a single oral dose of 40 ..mu..Ci of /sup 109/CdCl/sub 2/ laying hens were fed a practical type ration to which 0 or 60 ppm cadmium (Cd, As CdCl/sub 2/) was added. On the basis of /sup 109/Cd in excrement, apparent absorption of the isotope averaged less than 10% of the dose for both diets. Less than 4% of the dose was retained in total body tissue 23 days after dosing. Dietary Cd level did not significantly influence excretion of /sup 109/Cd by hens, but hens fed 60 ppm Cd retained a significantly higher proportion of /sup 109/Cd dose in liver, kidneys and whole body than did control hens. /sup 109/Cd was only detected in blood 48 hours after dosing and more than 75% of radioactivity in the blood occurred in plasma. Hens fed 60 ppm Cd consumed less feed and produced less eggs than control hens. /sup 109/Cd was found infrequently at very low levels in yolks of eggs produced by hens fed 60 ppm Cd. No radioactivity was detected in any egg whites, or in yolks of eggs produced by control hens.
Relation between the stable carbon isotope composition of fiddler crabs, plants, and soils in a salt marsh1

The fiddler crab Uca pugnax consumes detrital material on the soil surface in monospecific and mixed species stands of C3 and C4 plants in Georgia salt marshes. The carbon isotopic ratios of U. pugnax collected in eight separate areas of a salt marsh were linearly related to the 13C : 12C ratios of the plants; the relation between the 13C : 12C ratios of the crabs and marsh soils was less direct. The stable isotopic composition of the crab carbon was biased toward the 13C : 12C ratios of the C4 plants.
Intracellular protein degradation in cultured bovine lens epithelial cells.

Although several proteases have been identified in homogenates of cultured epithelial cells of the eye lens and in lens tissues, there is little information regarding intracellular protein degradation in intact lens cells in vitro. Cultured lens cells may be useful in the study of intracellular protein degradation in the lens, a tissue with a wide range of protein half-lives. This is of interest because alterations in protein turnover in the lens have been implicated in cataract formation. This study examines intracellular protein degradation in cultured bovine lens epithelial cells (BLEC). Cell cultures were incubated with radiolabeled leucine to label intracellular proteins. Protein degradation was measured by monitoring the release of trichloroacetic-acid-soluble radioactivity into the culture medium. The average half-life of long-lived proteins (half-life >50 h) was typically about 57 h in serum-supplemented medium. Average rates of degradation of long-lived proteins increased by up to 73% when fetal bovine serum was withdrawn from the culture medium. Serum had no effect on the degradation of short-lived proteins (half-life <10 h). Degradation of long-lived proteins in the presence and absence of serum was further studied in cultured BLEC from population doubling level (PDL) 2 to 43. Average half-life of proteins in serum-supplemented medium was 52 to 58 h and did not vary significantly as a function of PDL. Degradation rates in serum-free medium increased approximately twofold up to PDL 7, but returned by PDL 25 to original levels, which were maintained through PDL 43.
Temporary and permanent noise-induced changes in distortion product otoacoustic emissions in CBA/CaJ mice

Abstract A number of studies have shown that the ear can be protected from sound over-exposure, either by activating the cochlear efferent system, or by sound ‘conditioning’ in which the role of the efferent system is less certain. To study more definitively the molecular basis of deliberately induced cochlear protection from excessive sounds, it is advantageous to determine, for an inbred mouse strain, a range of noise exposure parameters that effectively alter cochlear function. As an initial step towards this goal, young CBA/CaJ mice were exposed to a 105-dB SPL octave-band noise (OBN), centered at 10 kHz, for various lengths of time consisting of 10 min, or 0.5, 1, 3, or 6 h. Distortion product otoacoustic emissions (DPOAEs) at the 2f1−f2 frequency, in response to equilevel primary tones of low to moderate levels, were used to quantify the damaging effects of these sound over-exposures on cochlear function. In addition, staining for acetylcholinesterase (AChE) activity to assess for noise-induced changes in the pattern of efferent-nerve innervation to the cochlea was also performed in a subset of mice that were exposed to the longest-lasting 6-h OBN. The 10-min OBN resulted in only temporary reductions in DPOAE levels, which recovered to pre-exposure values within 5 days. Increasing the exposure to 0.5 h resulted in permanent DPOAE losses that, for low primary-tone levels, were still present at 31 days post-exposure. Additionally, the 1-h and longer exposures caused permanent reductions in DPOAEs for all test levels, which were measurable at 31 days following exposure. Light-microscopic observations restricted to the 11–18-kHz frequency region of the organ of Corti, for a subset of mice exposed to the 6-h OBN, uncovered a significant loss of outer hair cells (OHCs). However, despite the OHC loss in this region, the AChE activity associated with the related pattern of efferent innervation remained largely intact.
Rational use of analgesic combinations

Careful selection of an effective analgesic regimen based on the amount and type of pain the patient is expected to have can prevent the stress and anxiety associated with breakthrough pain. When analgesics fail, it is not unusual for patients to go to desperate lengths to seek relief. The clinician can and should develop a variety of effective, safe analgesic regimens based on estimates of anticipated pain intensity that apply sound pharmacologic principles.